Review

A recipe for myositis: nuclear factor κB and nuclear factor of activated T-cells transcription factor pathways spiced up by cytokines

  • Received: 18 May 2017 Accepted: 09 July 2017 Published: 17 July 2017
  • Nuclear factor κB (NF-κB) is a well-known pro-inflammatory transcription factor that regulates the expression of the tissue’s immune-active components, which include cytokines, chemokines and adhesion molecules. In addition, the versatile nuclear factor of activated T-cells (NFAT) family of transcription factors plays a crucial role in the development and function of the immune system, integrating calcium signaling with other signaling pathways. NF-κB and NFAT share many structural and functional characteristics and likely regulate gene expression through shared enhancer elements. This review describes recent research data that has led to new insights into the involvement of NFκB- and NFAT-mediated pathways in the different idiopathic inflammatory myopathies. The general activation of NF-κB p65 in blood vessel endothelium, seems to flag down inflammatory cells that subsequently accumulate mostly at perimysial sites in dermatomyositis. The joint activation of p65 and NFAT5 in myofibers specifically at perifascicular areas reflects the characteristic tissue damage pattern observed in that particular subgroup of patients. In immune cells actively invading nonnecrotic muscle fibers in polymyositis and sporadic inclusion body myositis on the other hand, p65 activation is an important aspect of their cytotoxic and chemoattactant properties. In addition, both transcription factor families are generally upregulated in regenerating muscle fibers as components of the differentiation process. It can be concluded that the two transcription factor families function in close relationship with each other, representing two-edged swords for muscle disease: on the one hand promoting cell growth and regeneration, while on the other hand actively participating in inflammatory cell damage. In this respect, cytokines function as important go-betweens at the crossroads of the pathways. Beyond NF-κB and NFAT, many fascinating winding roads relevant to inflammatory myopathy disease management still lie ready for the exploring.

    Citation: Boel De Paepe. A recipe for myositis: nuclear factor κB and nuclear factor of activated T-cells transcription factor pathways spiced up by cytokines[J]. AIMS Allergy and Immunology, 2017, 1(1): 31-42. doi: 10.3934/Allergy.2017.1.31

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  • Nuclear factor κB (NF-κB) is a well-known pro-inflammatory transcription factor that regulates the expression of the tissue’s immune-active components, which include cytokines, chemokines and adhesion molecules. In addition, the versatile nuclear factor of activated T-cells (NFAT) family of transcription factors plays a crucial role in the development and function of the immune system, integrating calcium signaling with other signaling pathways. NF-κB and NFAT share many structural and functional characteristics and likely regulate gene expression through shared enhancer elements. This review describes recent research data that has led to new insights into the involvement of NFκB- and NFAT-mediated pathways in the different idiopathic inflammatory myopathies. The general activation of NF-κB p65 in blood vessel endothelium, seems to flag down inflammatory cells that subsequently accumulate mostly at perimysial sites in dermatomyositis. The joint activation of p65 and NFAT5 in myofibers specifically at perifascicular areas reflects the characteristic tissue damage pattern observed in that particular subgroup of patients. In immune cells actively invading nonnecrotic muscle fibers in polymyositis and sporadic inclusion body myositis on the other hand, p65 activation is an important aspect of their cytotoxic and chemoattactant properties. In addition, both transcription factor families are generally upregulated in regenerating muscle fibers as components of the differentiation process. It can be concluded that the two transcription factor families function in close relationship with each other, representing two-edged swords for muscle disease: on the one hand promoting cell growth and regeneration, while on the other hand actively participating in inflammatory cell damage. In this respect, cytokines function as important go-betweens at the crossroads of the pathways. Beyond NF-κB and NFAT, many fascinating winding roads relevant to inflammatory myopathy disease management still lie ready for the exploring.


    The inequalities discovered by C. Hermite and J. Hadamard for convex functions are considerable significant in the literature (see, e.g., [9], [18], [27,p.137]). These inequalities state that if f:IR is a convex function on the interval I of real numbers and a,bI with a<b, then

    f(a+b2)1babaf(x)dxf(a)+f(b)2. (1.1)

    Both inequalities hold in the reversed direction if f is concave.

    The Hermite-Hadamard inequality, which is the first fundamental result for convex mappings with a natural geometrical interpretation and many applications, has drawn attention much interest in elementary mathematics. A number of mathematicians have devoted their efforts.

    The most well-known inequalities related to the integral mean of a convex function are the Hermite Hadamard inequalities or its weighted versions, the so-called Hermite-Hadamard-Fejér inequalities. In [17], Fejer gave a weighted generalization of the inequalities (1.1) as the following:

    Theorem 1. f:[a,b]R, be a convex function, then the inequality

    f(a+b2)bag(x)dxbaf(x)g(x)dxf(a)+f(b)2bag(x)dx (1.2)

    holds, where g:[a,b]R is nonnegative, integrable, and symmetric about x=a+b2 (i.e. g(x)=g(a+bx)).

    In this paper we will establish some new Fejér type inequalities for the new concept of co-ordinated hyperbolic ρ-convex functions.

    The overall structure of the paper takes the form of four sections including introduction. The paper is organized as follows: we first give the definition of co-ordinated convex functions, the definition of fractional integrals and related Hermite-Hadamard inequality in Section 1. We also recall the concept of hyperbolic ρ-convex functions and co-ordinated hyperbolic ρ-convex functions introduced by Özçelik et. al in [23]. Moreover, we give a lemma and a theorem which will be frequently used in the next section. Some Hermite-Hadamard-Fejer type inequalities for co-ordinated hyperbolic ρ-convex functions are obtained and some special cases of the results are also given in Section 2. Then, we also apply the inequalities obtained in Section 2 to establish some fractional Fejer type inequalities in Section 3. Finally, in Section 4, some conclusions and further directions of research are discussed.

    A formal definition for co-ordinated convex function may be stated as follows:

    Definition 1. A function f:Δ:=[a,b]×[c,d]R is called co-ordinated convex on Δ, for all (x,u),(y,v)Δ and t,s[0,1], if it satisfies the following inequality:

    f(tx+(1t) y,su+(1s) v)ts f(x,u)+t(1s)f(x,v)+s(1t)f(y,u)+(1t)(1s)f(y,v). (1.3)

    The mapping f is a co-ordinated concave on Δ if the inequality (1.3) holds in reversed direction for all t,s[0,1] and (x,u),(y,v)Δ.

    In [11], Dragomir proved the following inequalities which is Hermite-Hadamard type inequalities for co-ordinated convex functions on the rectangle from the plane R2.

    Theorem 2. Suppose that f:Δ:=[a,b]×[c,d]R is co-ordinated convex, then we have the following inequalities:

    f(a+b2,c+d2)12[1babaf(x,c+d2)dx+1dcdcf(a+b2,y)dy]1(ba)(dc)badcf(x,y)dydx14[1babaf(x,c)dx+1babaf(x,d)dx+1dcdcf(a,y)dy+1dcdcf(b,y)dy]f(a,c)+f(a,d)+f(b,c)+f(b,d)4. (1.4)

    The above inequalities are sharp. The inequalities in (1.4) hold in reverse direction if the mapping f is a co-ordinated concave mapping.

    Over the years, the numerous studies have focused on to establish generalization of the inequality (1.1) and (1.4). For some of them, please see ([1,2,3,4,5,6,7,8], [19,20,21,22,23,24,25,26], [28,29,30,31,32,33,34,35,36]).

    Definition 2. [29] Let fL1(Δ).The Riemann-Lioville integrals Jα,βa+,c+,Jα,βa+,d,+Jα,βb,c+ and Jα,βb,dof order α,β>0 with a,c0 are defined by

    Jα,βa+,c+f(x,y)=1Γ(α)Γ(β)xayc(xt)α1(ys)β1f(t,s)dsdt,  x>a, y>c,Jα,βa+,df(x,y)=1Γ(α)Γ(β)xady(xt)α1(sy)β1f(t,s)dsdt,  x>a, y>d,Jα,βb,c+f(x,y)=1Γ(α)Γ(β)bxyc(tx)α1(ys)β1f(t,s)dsdt,  x<b, y>c,Jα,βb,df(x,y)=1Γ(α)Γ(β)bxdy(tx)α1(sy)β1f(t,s)dsdt,  x<b, y<d,

    respectively. Here, Γ is the Gamma funtion,

    J0,0a+,c+f(x,y)=J0,0a+,df(x,y)=J0,0b,c+f(x,y)=J0,0b,df(x,y)

    and

    J1,1a+,c+f(x,y)=xaycf(t,s)dsdt.

    First, we give the definition of hyperbolic ρ-convex functions and some related inequalities. Then we define the co-ordinated hyperbolic ρ -convex functions.

    Definition 3. [10] A function f:IR is said to be hyperbolic ρ-convex, if for any arbitrary closed subinterval [a,b] of I such that we have

    f(x)sinh[ρ(bx)]sinh[ρ(ba)]f(a)+sinh[ρ(xa)]sinh[ρ(ba)]f(b) (1.5)

    for all x[a,b]. If we take x=(1t)a+tb, t[0,1] in (1.5), then the condition (1.5) becomes

    f((1t)a+tb)sinh[ρ(1t)(ba)]sinh[ρ(ba)]f(a)+sinh[ρt(ba)]sinh[ρ(ba)]f(b). (1.6)

    If the inequality (1.5) holds with "", then the function will be called hyperbolic ρ-concave on I.

    The following Hermite-Hadamard inequality for hyperbolic ρ-convex function is proved by Dragomir in [10].

    Theorem 3. Suppose that f:IR is hyperbolic ρ-convex on I. Then for any a,bI, we have

    2ρf(a+b2)sinh[ρ(ba)2]baf(x)dxf(a)+f(b)ρtanh[ρ(ba)2]. (1.7)

    Moreover in [12], Dragomir prove the following Hermite Hadamard-Fejer type inequalities for hyperbolic ρ-convex functions.

    Theorem 4. Assume that the function f:IR is hyperbolic ρ-convex on I and a,bI. Assume also that p:[a,b]R is a positive, symmetric and integrable function on [a,b], then we have

    f(a+b2)bacosh[ρ(xa+b2)]p(x)dxbaf(x)p(x)dxf(a)+f(b)2sech[ρ(ba)2]bacosh[ρ(xa+b2)]p(x)dx. (1.8)

    For the other inequalities for hyperbolic ρ-convex functions, please refer to ([12,13,14,15]).

    Now we give the definition of co-ordinated hyperbolic ρ-convex functions.

    Definition 4. [23] A function f:ΔR is said to co-ordinated hyperbolic ρ-convex on Δ, if the inequality

    f(x,y)sinh[ρ1(bx)]sinh[ρ1(ba)]sinh[ρ2(dy)]sinh[ρ2(dc)]f(a,c)+sinh[ρ1(bx)]sinh[ρ1(ba)]sinh[ρ2(yc)]sinh[ρ2(dc)]f(a,d)+sinh[ρ1(xa)]sinh[ρ1(ba)]sinh[ρ2(dy)]sinh[ρ2(dc)]f(b,c)+sinh[ρ1(xa)]sinh[ρ1(ba)]sinh[ρ2(yc)]sinh[ρ2(dc)]f(b,d). (1.9)

    holds.

    If the inequality (1.9) holds with "", then the function will be called co-ordinated hyperbolic ρ-concave on Δ.

    If we take x=(1t)a+tb and y=(1s)c+sd for t,s,[0,1], then the inequality (1.9) can be written as

    f((1t)a+tb,(1s)c+sd)sinh[ρ1(1t)(ba)]sinh[ρ1(ba)]sinh[ρ2(1s)(dy)]sinh[ρ2(dc)]f(a,c)+sinh[ρ1(1t)(ba)]sinh[ρ1(ba)]sinh[ρ2s(dy)]sinh[ρ2(dc)]f(a,d)+sinh[ρ1t(ba)]sinh[ρ1(ba)]sinh[ρ2(1s)(dy)]sinh[ρ2(dc)]f(b,c)+sinh[ρ1(ba)]sinh[ρ1(ba)]sinh[ρ2s(dy)]sinh[ρ2(dc)]f(b,d). (1.10)

    Now we give the following useful lemma:

    Lemma 1. [23] If f:Δ=[a,b]×[c,d]R is co-ordinated ρ-convex function on Δ, then we have the following inequality

    cosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]f(a+b2,c+d2)14[f(x,y)+f(x,c+dy)+f(a+bx,y)+f(a+bx,c+dy)]f(a,c)+f(a,d)+f(b,c)+f(b,d)4cosh[ρ1(xa+b2)]cosh[ρ1(ba)2]cosh[ρ2(yc+d2)]cosh[ρ2(dc)2] (1.11)

    for all (x,y)Δ.

    Theorem 5. Let p:ΔR be a positive, integrable and symmetric about a+b2 and c+d2. Let, f:ΔR be a co-ordinated hyperbolic ρ-convex functions on Δ. We have the following Hermite-Hadamard-Fejer type inequalities:

    f(a+b2,c+d2)badccosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]p(x,y)dydxbadcf(x,y)p(x,y)dydxf(a,c)+f(a,d)+f(b,c)+f(b,d)4cosh[ρ1(ba)2]cosh[ρ2(dc)2]×badccosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]p(x,y)dydx. (2.1)

    Proof. Multiplying the inequality (1.1) by p(x,y)>0 and then integrating with respect to (x,y) on Δ, we obtain

    f(a+b2,c+d2)badccosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]p(x,y)dydx14badc[f(x,y)+f(x,c+dy)+f(a+bx,y)+f(a+bx,c+dy)]p(x,y)dydxf(a,c)+f(a,d)+f(b,c)+f(b,d)4cosh[ρ1(ba)2]cosh[ρ2(dc)2]×badccosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]p(x,y)dydx (2.2)

    Since p is symmetric about a+b2 and c+d2, one can show that

    badcf(x,c+dy)p(x,y)dydx=badcf(a+bx,y)p(x,y)dydx=badcf(a+bx,c+dy)p(x,y)dydx=badcf(x,y)p(x,y)dydx.

    This completes the proof.

    Remark 1. If we choose p(x,y)=1 in Theorem 5, then we have the following the inequality

    4ρ1ρ2sinh[ρ1(ba)2]sinh[ρ2(dc)2]f(a+b2,c+d2)badcf(x,y)dydxf(a,c)+f(a,d)+f(b,c)+f(b,d)ρ1ρ2tanh[ρ1(ba)2]tanh[ρ2(dc)2]

    which is proved by Özçelik et. al in [23].

    Corollary 1. Suppose that all assumptions of Theorem 5 are satisfied. Then we have the following inequality,

    f(a+b2,c+d2)badcw(x,y)dydxbadcf(x,y)w(x,y)sech[ρ1(xa+b2)]sech[ρ2(yc+d2)]dydxf(a,c)+f(a,d)+f(b,c)+f(b,d)4sech[ρ1(ba)2]sech[ρ2(dc)2]badcw(x,y)dydx. (2.3)

    Proof. Let us define the function p(x,y) by

    w(x,y)=p(x,y)cosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)].

    Clearly, w(x.y) is a a positive, integrable and symmetric about a+b2 and c+d2. If we apply Theorem 5 for the function w(x,y) then we establish the desired inequality (2.3).

    Remark 2. If we choose w(x,y)=1 for all (x,y)ϵΔ in Corollary 1, then we have the following the inequality

    f(a+b2,c+d2)1(ba)(dc)badcf(x,y)sech[ρ1(xa+b2)]sech[ρ2(yc+d2)]dydxf(a,c)+f(a,d)+f(b,c)+f(b,d)4sech[ρ1(ba)2]sech[ρ2(dc)2]. (2.4)

    which is proved by Özçelik et. al in [23].

    Theorem 6. Let p:ΔR be a positive, integrable and symmetric about a+b2 and c+d2. Let f:ΔR be a co-ordinated hyperbolic ρ-convex on Δ, then we have the following Hermite-Hadamard-Fejer type inequalities

    f(a+b2,c+d2)badccosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]p(x,y)dydx12[badcf(x,c+d2)cosh[ρ2(yc+d2)]p(x,y)dydx+badcf(a+b2,y)cosh[ρ1(xa+b2)]p(x,y)dydx]badcf(x,y)p(x,y)dydx14[sech[ρ2(dc)2]badc[f(x,c)+f(x,d)]cosh[ρ2(yc+d2)]p(x,y)dydx+sech[ρ1(ba)2]badc[f(a,y)+f(b,y)]cosh[ρ1(xa+b2)]p(x,y)dydx]f(a,c)+f(b,c)+f(a,d)+f(b,d)4sech[ρ1(ba)2]sech[ρ2(dc)2]×badccosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]p(x,y)dydx. (2.5)

    Proof. Since f is co-ordinated hyperbolic ρ-convex on Δ, if we define the mappings fx:[c,d]R, fx(y)=f(x,y) and px:[c,d]R, px(y)=p(x,y), then fx(y) is hyperbolic ρ-convex on [c,d] and px(y) is positive, integrable and symmetric about c+d2 for all x[a,b]. If we apply the inequality (1.8) for the hyperbolic ρ-convex function fx(y), then we have

    fx(c+d2)dccosh[ρ2(yc+d2)]px(y)dydcfx(y)px(y)dyfx(c)+fx(d)2sech[ρ2(dc)2]dccosh[ρ2(yc+d2)]px(y)dy. (2.6)

    That is,

    f(x,c+d2)dccosh[ρ2(yc+d2)]p(x,y)dydcf(x,y)p(x,y)dyf(x,c)+f(x,d)2sech[ρ2(dc)2]dccosh[ρ2(yc+d2)]p(x,y)dy. (2.7)

    Integrating the inequality (2.7) with respect to x from a to b, we obtain

    badcf(x,c+d2)cosh[ρ2(yc+d2)]p(x,y)dydxbadcf(x,y)p(x,y)dydx12badc[f(x,c)+f(x,d)]sech[ρ2(dc)2]cosh[ρ2(yc+d2)]p(x,y)dydx. (2.8)

    Similarly, as f is co-ordinated hyperbolic ρ-convex on Δ, if we define the mappings fy:[a,b]R, fy(x)=f(x,y) and py:[a,b]R, py(x)=p(x,y), then fy(x) is hyperbolic ρ-convex on [a,b] and py(x) is positive, integrable and symmetric about a+b2 for all y[c,d]. Utilizing the inequality (1.8) for the hyperbolic ρ-convex function fy(x), then we obtain the inequality

    fy(a+b2)bacosh[ρ1(xa+b2)]py(x)dxbafy(x)py(x)dxfy(a)+fy(b)2sech[ρ1(ba)2]bacosh[ρ1(xa+b2)]py(x)dx (2.9)

    i.e.

    f(a+b2,y)bacosh[ρ1(xa+b2)]p(x,y)dxbaf(x,y)p(x,y)dxf(a,y)+f(b,y)2sech[ρ1(ba)2]bacosh[ρ1(xa+b2)]p(x,y)dx. (2.10)

    Integrating the inequality (2.10) with respect to y on [c,d], we get

    badcf(a+b2,y)cosh[ρ1(xa+b2)]p(x,y)dydxbadcf(x,y)p(x,y)dydx12badc[f(a,y)+f(b,y)]sech[ρ1(ba)2]cosh[ρ1(xa+b2)]p(x,y)dydx. (2.11)

    Summing the inequalities (2.8) and (2.11), we obtain the second and third inequalities in (2.5).

    Since f(a+b2,y) is hyperbolic ρ-convex on [c,d] and px(y) is positive, integrable and symmetric about c+d2, using the first inequality in (1.8), we have

    f(a+b2,c+d2)dccosh[ρ2(yc+d2)]p(x,y)dydcf(a+b2,y)p(x,y)dy. (2.12)

    Multiplying the inequality (2.12) by cosh[ρ1(xa+b2)] and integrating resulting inequality with respect to x on [a,b], we get

    f(a+b2,c+d2)badccosh[ρ2(yc+d2)]cosh[ρ1(xa+b2)]p(x,y)dydxbadcf(a+b2,y)cosh[ρ1(xa+b2)]p(x,y)dydx. (2.13)

    Since f(x,c+d2) is hyperbolic ρ-convex on [a,b] and py(x) is positive, integrable and symmetric about a+b2, utilizing the first inequality in (1.8), we have the following inequality

    f(a+b2,c+d2)bacosh[ρ1(xa+b2)]p(x,y)dxbaf(x,c+d2)p(x,y)dx. (2.14)

    Multiplying the inequality (2.14) by cosh[ρ2(yc+d2)] and integrating resulting inequality with respect to y on [c,d], we get

    f(a+b2,c+d2)badccosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]p(x,y)dydxbadcf(x,c+d2)cosh[ρ2(yc+d2)]p(x,y)dydx. (2.15)

    From the inequalities (2.13) and (2.15), we obtain the first inequality in (2.5).

    For the proof of last inequality in (2.5), using the second inequality in (1.8) for the hyperbolic ρ-convex functions f(x,c) and f(x,d) on [a,b] and for the symmetric function py(x), we obtain the inequalities

    baf(x,c)p(x,y)dxf(a,c)+f(b,c)2sech[ρ1(ba)2]bacosh[ρ1(xa+b2)]p(x,y)dx (2.16)

    and

    baf(x,d)p(x,y)dxf(a,d)+f(b,d)2sech[ρ1(ba)2]bacosh[ρ1(xa+b2)]p(x,y)dx. (2.17)

    If we multiply the inequalities (2.16) and (2.17) by sech[ρ2(dc)2]cosh[ρ2(yc+d2)] and integrating the resulting inequalities on [c,d], then we have

    badcf(x,c)sech[ρ2(dc)2]cosh[ρ2(yc+d2)]p(x,y)dydxf(a,c)+f(b,c)2sech[ρ1(ba)2]sech[ρ2(dc)2]×badccosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]p(x,y)dydx (2.18)

    and

    badcf(x,d)sech[ρ2(dc)2]cosh[ρ2(yc+d2)]p(x,y)dydxf(a,d)+f(b,d)2sech[ρ1(ba)2]sech[ρ2(dc)2]×badccosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]p(x,y)dydx. (2.19)

    Similarly, applying the second inequality in (1.8) for the hyperbolic ρ-convex functions f(a,y) and f(b,y) on [c,d] and for the symmetric function px(y), we have

    dcf(a,y)p(x,y)dyf(a,c)+f(a,d)2sech[ρ2(dc)2]dccosh[ρ2(yc+d2)]p(x,y)dy (2.20)

    and

    dcf(b,y)p(x,y)dyf(b,c)+f(b,d)2sech[ρ2(dc)2]dccosh[ρ2(yc+d2)]p(x,y)dy. (2.21)

    Multiplying the inequalities (2.20) and (2.21) by sech[ρ1(ba)2]cosh[ρ1(xa+b2)] and integrating the resulting inequalities on [a,b], then we have

    badcf(a,y)sech[ρ1(ba)2]cosh[ρ1(xa+b2)]p(x,y)dydxf(a,c)+f(a,d)2sech[ρ2(dc)2]sech[ρ1(ba)2]×badccosh[ρ2(yc+d2)]cosh[ρ1(xa+b2)]p(x,y)dydx (2.22)

    and

    badcf(b,y)sech[ρ1(ba)2]cosh[ρ1(xa+b2)]p(x,y)dydxf(b,c)+f(b,d)2sech[ρ2(dc)2]sech[ρ1(ba)2]×badccosh[ρ2(yc+d2)]cosh[ρ1(xa+b2)]p(x,y)dydx. (2.23)

    Summing the inequalities (2.18), (2.19), (2.22) and (2.23), we establish the last inequality in (2.5). This completes the proof.

    Remark 3. If we choose p(x,y)=1 in Theorem 6, then we have

    4ρ1ρ2sinh[ρ1(ba)2]sinh[ρ2(dc)2]f(a+b2,c+d2)1ρ1sinh[ρ1(ba)2]dcf(a+b2,y)dy+1ρ2sinh[ρ2(dc)2]baf(x,c+d2)dxbadcf(x,y)dydx12[1ρ2tanh[ρ2(dc)2]ba[f(x,c)+f(x,d)]dx+1ρ1tanh[ρ1(ba)2]dc[f(a,y)+f(b,y)]dy]tanh[ρ1(ba)2]tanh[ρ2(dc)2]f(a,c)+f(a,d)+f(b,c)+f(b,d)ρ1ρ2 (2.24)

    which is proved by Özçelik et. al in [23].

    Remark 4. Choosing ρ1=ρ2=0 in Theorem 6, we obtain

    f(a+b2,c+d2)badcp(x,y)dydx12badc[f(x,c+d2)+f(a+b2,y)]p(x,y)dydxbadcf(x,y)p(x,y)dydx14badc[f(x,c)+f(x,d)+f(a,y)+f(b,y)]p(x,y)dydxf(a,c)+f(a,d)+f(b,c)+f(b,d)4badcp(x,y)dydx.

    which is proved by Budak and Sarikaya in [5].

    Corollary 2. Let g1:[a,b]R and g1:[c,d]R be two positive, integrable and symmetric about a+b2 and c+d2, respectively. If we choose p(x,y)=g1(x)g2(y)G1G2 for all (x,y)Δ in Theorem 6, then we have

    f(a+b2,c+d2)12[1G1baf(x,c+d2)g1(x)dx+1G2dcf(a+b2,y)g2(y)dy]1G1G2badcf(x,y)g1(x)g2(y)dydx14[sech[ρ2(dc)2]1G1ba[f(x,c)+f(x,d)]g1(x)dx+sech[ρ1(ba)2]1G2dc[f(a,y)+f(b,y)]g2(y)dy]f(a,c)+f(b,c)+f(a,d)+f(b,d)4sech[ρ1(ba)2]sech[ρ2(dc)2] (2.25)

    where

    G1=bacosh[ρ1(xa+b2)]g1(x)dxandG2=dccosh[ρ2(yc+d2)]g2(y)dy.

    Remark 5. If we choose ρ1=ρ2=0 in Corollary 2, then we have

    f(a+b2,c+d2)12[1G1baf(x,c+d2)g1(x)dx+1G2dcf(a+b2,y)g2(y)dy]1G1G2badcf(x,y)g1(x)g2(y)dydx14[1G1ba[f(x,c)+f(x,d)]g1(x)dx+1G2dc[f(a,y)+f(b,y)]g2(y)dy]f(a,c)+f(a,d)+f(b,c)+f(b,d)4

    which is proved by Farid et al. in [16].

    In this section we obtain some fractional Hermite-Hadamard an Fejer type inequalities for co-ordinated hyperbolic ρ-convex functions.

    Theorem 7. If f:ΔR is a co-ordinated hyperbolic ρ-convex functions on Δ, then we have the following Hermite-Hadamard and Fejer type inequalities,

    f(a+b2,c+d2)H(α,β)[Jα,βa+,c+f(b,d)+Jα,βa+,df(b,c)+Jα,βb,c+f(a,d)+Jα,βb,df(a,c)]f(a,c)+f(a,d)+f(b,c)+f(b,d)4sech[ρ1(ba)2]sech[ρ2(dc)2]H(α,β)

    where

    H(α,β)=1Γ(α)Γ(β)badccosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]×[(bx)α1(dy)β1+(bx)α1(yc)β1+(xa)α1(dy)β1+(xa)α1(yc)β1]dydx.

    Proof. If we apply Theorem 5 for the symmetric function

    p(x,y)=1Γ(α)Γ(β)[(bx)α1(dy)β1+(bx)α1(yc)β1+(xa)α1(dy)β1+(xa)α1(yc)β1],

    then we get the following inequality

    f(a+b2,c+d2)H(α,β)1Γ(α)Γ(β)badcf(x,y)[(bx)α1(dy)β1+(bx)α1(yc)β1+(xa)α1(dy)β1+(xa)α1(yc)β1]dydxf(a,c)+f(a,d)+f(b,c)+f(b,d)4sech[ρ1(ba)2]sech[ρ2(dc)2]H(α,β).

    From the definition of the double fractional integrals we have

    1Γ(α)Γ(β)badcf(x,y)[(bx)α1(dy)β1+(bx)α1(yc)β1+(xa)α1(dy)β1+(xa)α1(yc)β1]dydx=[Jα,βa+,c+f(b,d)+Jα,βa+,df(b,c)+Jα,βb,c+f(a,d)+Jα,βb,df(a,c)]

    which completes the proof.

    Remark 6. If we choose ρ1=ρ2=0 in Theorem 7, then we have the following fractional Hermite-Hadamard inequality,

    f(a+b2,c+d2)Γ(α+1)Γ(β+1)4(ba)α(dc)β[Jα,βa+,c+f(b,d)+Jα,βa+,df(b,c)+Jα,βb,c+f(a,d)+Jα,βb,df(a,c)]f(a,c)+f(a,d)+f(b,c)+f(b,d)4

    which was proved by Sarikaya in [29,Theorem 4].

    Remark 7. If we choose α =β=1 in Theorem 7, then we have

    H(1,1)=16ρ1ρ2sinh(ρ1(ba)2)sinh(ρ2(dc)2).

    Thus, we get the following Hermite-Hadamard inequality,

    4ρ1ρ2f(a+b2,c+d2)sinh(ρ1(ba)2)sinh(ρ2(dc)2)badcf(x,y)dydxf(a,c)+f(a,d)+f(b,c)+f(b,d)ρ1ρ2tanh[ρ1(ba)2]tanh[ρ2(dc)2]

    which is proved by Özçelik et al. in [23].

    Theorem 8. Let p:ΔR be a positive, integrable and symmetric about a+b2 and c+d2. If f:ΔR is a co-ordinated hyperbolic ρ-convex functions on Δ, then we have the following Hermite-Hadamard-Fejer type inequalities,

    f(a+b2,c+d2)Hp(α,β)[Jα,βa+,c+(fp)(b,d)+Jα,βa+,d(fp)(b,c)+Jα,βb,c+(fp)(a,d)+Jα,βb,d(fp)(a,c)]f(a,c)+f(a,d)+f(b,c)+f(b,d)4sech[ρ1(ba)2]sech[ρ2(dc)2]Hp(α,β)

    where

    Hp(α,β)=1Γ(α)Γ(β)badccosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]×[(bx)α1(dy)β1+(bx)α1(yc)β1+(xa)α1(dy)β1+(xa)α1(yc)β1]p(x,y)dydx.

    Proof. Let us define the function k(x,y) by

    k(x,y)=p(x,y)Γ(α)Γ(β)[(bx)α1(dy)β1+(bx)α1(yc)β1+(xa)α1(dy)β1+(xa)α1(yc)β1],

    Clearly, k(x.y) is a a positive, integrable and symmetric about a+b2 and c+d2. If we apply Theorem 5 for the function k(x,y) then we obtain,

    f(a+b2,c+d2)Hp(α,β)1Γ(α)Γ(β)badcf(x,y)p(x,y)[(bx)α1(dy)β1+(bx)α1(yc)β1+(xa)α1(dy)β1+(xa)α1(yc)β1]dydxf(a,c)+f(a,d)+f(b,c)+f(b,d)4cosh[ρ1(ba)2]cosh[ρ2(dc)2]Hp(α,β).

    From the definition of the double fractional integrals we have

    1Γ(α)Γ(β)badcf(x,y)[(bx)α1(dy)β1+(bx)α1(yc)β1+(xa)α1(dy)β1+(xa)α1(yc)β1]p(x,y)dydx=[Jα,βa+,c+(fp)(b,d)+Jα,βa+,d(fp)(b,c)+Jα,βb,c+(fp)(a,d)+Jα,βb,d(fp)(a,c)].

    This completes the proof.

    Remark 8. If we choose ρ1=ρ2=0 in Theorem 3, then we have the following fractional Hermite-Hadamard inequality,

    f(a+b2,c+d2)[Jα,βa+,c+p(b,d)+Jα,βa+,dp(b,c)+Jα,βb,c+p(a,d)+Jα,βb,dp(a,c)][Jα,βa+,c+(fp)(b,d)+Jα,βa+,d(fp)(b,c)+Jα,βb,c+(fp)(a,d)+Jα,βb,d(fp)(a,c)]f(a,c)+f(a,d)+f(b,c)+f(b,d)4[Jα,βa+,c+p(b,d)+Jα,βa+,dp(b,c)+Jα,βb,c+p(a,d)+Jα,βb,dp(a,c)]

    which is proved by Yaldız et all in [34].

    Remark 9. If we choose α =β=1 in Theorem 3, then we have Theorem 1.3 reduces to Theorem 5.

    Theorem 9. If f:ΔR is a co-ordinated hyperbolic ρ-convex functions on Δ. Then we have the following Hermite-Hadamard type inequalities for fractional integrals,

    f(a+b2,c+d2)H1(α,β)12[(Jαa+f(b,c+d2)+Jαbf(a,c+d2))H2(β)+Jβc+f(d,a+b2)+Jβdf(c,a+b2)H3(α)][Jα,βa+,c+f(b,d)+Jα,βa+,df(b,c)+Jα,βb,c+f(a,d)+Jα,βb,df(a,c)]14[sech[ρ2(dc)2](Jαa+f(b,c)+Jαa+f(b,d)+Jαbf(a,c)+Jαbf(a,d))H2(β)+sech[ρ1(ba)2](Jβc+f(a,d)+Jβc+f(b,d)+Jβdf(a,c)+Jβdf(b,c))H3(α)]f(a,c)+f(b,c)+f(a,d)+f(b,d)4sech[ρ1(ba)2]sech[ρ2(dc)2]H1(α,β) (3.1)

    where

    H1(α,β)=1Γ(α)Γ(β)badccosh[ρ1(xa+b2)]cosh[ρ2(yc+d2)]×[(bx)α1(dy)β1+(bx)α1(yc)β1+(xa)α1(dy)β1+(xa)α1(yc)β1]dydx,
    H2(β)=1Γ(β)dccosh[ρ2(yc+d2)][(dy)β1+(yc)β1]dy

    and

    H3(α,β)=1Γ(α)bacosh[ρ1(xa+b2)][(bx)α1+(xa)α1]dx.

    Proof. If we apply Theorem 6 for the symmetric function

    p(x,y)=1Γ(α)Γ(β)[(bx)α1(dy)β1+(bx)α1(yc)β1+(xa)α1(dy)β1+(xa)α1(yc)β1],

    then we get the following inequality

    f(a+b2,c+d2)H1(α,β)12[(1Γ(α)baf(x,c+d2)[(bx)α1+(xa)α1]dx)H2(β)+(1Γ(β)dcf(a+b2,y)[(dy)β1+(yc)β1]dy)H3(α)]1Γ(α)Γ(β)badcf(x,y)[(bx)α1(dy)β1+(bx)α1(yc)β1+(xa)α1(dy)β1+(xa)α1(yc)β1]dydx14[sech[ρ2(dc)2](1Γ(α)ba[f(x,c)+f(x,d)][(bx)α1+(xa)α1]dx)H2(β)+sech[ρ1(ba)2](1Γ(β)ba[f(a,y)+f(b,y)][(dy)β1+(yc)β1]dx)H3(α)]f(a,c)+f(b,c)+f(a,d)+f(b,d)4sech[ρ1(ba)2]sech[ρ2(dc)2]H1(α,β).

    This completes the proof.

    Remark 10. Under assumptions of Theorem 9 with α=β=1, the inequalities (3.1) reduce to inequalities (2.5) proved by Özçelik et. al in [23].

    Remark 11. Under assumptions of Theorem 9 with ρ1=ρ2=0, the inequalities (3.1) reduce to inequalities proved by Sarikaya in [29,Theorem 4]

    In this paper, we establish some Fejer type inequalities for co-ordinated hyperbolic ρ-convex functions. By using these inequalities we present some inequalities for Riemann-Liouville fractional integrals. In the future works, authors can prove similar inequalities for other fractional integrals.

    All authors declare no conflicts of interest.

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