Interleukin-17A Promotes Aortic Endothelial Cell Activation via Transcriptionally and Post-translationally Activating p38 Mitogen-activated Protein Kinase (MAPK) Pathway

Mai, Jietang; Nanayakkara, Gayani; Lopez-Pastraña, Jahaira; Li, Xinyuan; Li, Yafeng; Wang, Xin; Song, Ai Lin; Virtue, Anthony; Shao, Ying; Shan, Huimin; Liu, Fang; Autieri, Michael V.; Kunapuli, Satya P.; Iwakura, Yoichiro; Jiang, Xiaohua; Wang, Hong; Yang, Xiaofeng

doi:10.1074/jbc.m115.690081

Cited by 71 publications

(70 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note, recent reports attributed that LPA receptors may also initiate immune-suppressive signals [67–69] in addition to pro-inflammatory signals [70]. Similar conflicting results have been reported to pro-inflammatory mediators such as caspase-1 [71], anti-inflammatory estrogen [72] and pro-inflammatory cytokine interleukin-17 [73]. The contextual dependence of these biologicals systems that were used to study these inflammatory mediators may contribute to these dissimilarities observed [74].…”

Section: Discussionmentioning

confidence: 75%

Lysophospholipid Receptors, as Novel Conditional Danger Receptors and Homeostatic Receptors Modulate Inflammation—Novel Paradigm and Therapeutic Potential

Wang

Nanayakkara

et al. 2016

J. of Cardiovasc. Trans. Res.

Self Cite

View full text Add to dashboard Cite

There are limitations in the current classification of danger associated molecular patterns (DAMP) receptors. To overcome these limitations, we propose a new paradigm by using endogenous metabolites lysophospholipids (LPLs) as a prototype. By utilizing a data mining method we pioneered, we made the following findings: 1) Endogenous metabolites such as LPLs at basal level have physiological functions; 2) under sterile inflammation, expression of some LPLs are elevated. These LPLs act as conditional DAMPs or anti-inflammatory homeostasis-associated molecular pattern molecules (HAMPs) for regulating the progression of inflammation or inhibition of inflammation, respectively; 3) receptors for conditional DAMPs and HAMPs are differentially expressed in human and mouse tissues; and 4) complex signaling mechanism exists between pro-inflammatory mediators and classical DAMPs that regulate the expression of conditional DAMPs and HAMPs. This novel insight will facilitate identification of novel conditional DAMPs and HAMPs, thus promote development of new therapeutic targets to treat inflammatory disorders.

show abstract

Section: Discussionmentioning

confidence: 75%

Lysophospholipid Receptors, as Novel Conditional Danger Receptors and Homeostatic Receptors Modulate Inflammation—Novel Paradigm and Therapeutic Potential

Wang

Nanayakkara

et al. 2016

J. of Cardiovasc. Trans. Res.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Stromal cells that are similar to PCs in ontogeny, such as fibroblasts, may produce 20-fold more of IL-6 than human brain ECs after same dosage of IL-17 stimulation (10). Species differences may also be relevant as mouse aortic ECs are at least 10-fold more responsive to IL-17 than human aortic ECs (25). On the other hand, human lung microvascular ECs do appear to express IL-17RA and respond to IL-17 activation, although the magnitude of the responses observed while comparable to TNF in this cell type, are quite weak by comparisons to TNF responses in other studies (26, 27).…”

Section: Discussionmentioning

confidence: 99%

IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium

Liu

Lauridsen

Amezquita

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

A classical hallmark of acute inflammation is neutrophil infiltration of tissues, a multi-step process that involves sequential cell-cell interactions of circulating leukocytes with interleukin (IL)-1- or tumor necrosis factor-α (TNF)-activated microvascular endothelial cells (ECs) and pericytes (PCs) that form the wall of the postcapillary venules. The initial infiltrating cells accumulate perivascularly in close proximity to PCs. IL-17, a pro-inflammatory cytokine that acts on target cells via a heterodimeric receptor formed by IL-17RA and IL-17RC subunits, also promotes neutrophilic inflammation but its effects on vascular cells are less clear. We report that both cultured human ECs and PCs strongly express IL-17RC and, while neither cell type expresses much IL-17RA, PCs express significantly more than ECs. IL-17, alone or synergistically with TNF, significantly alters inflammatory gene expression in cultured human PCs but not ECs. RNA-seq analysis identifies many IL-17-induced transcripts in PCs encoding proteins known to stimulate neutrophil-mediated immunity. Conditioned media (CM) from IL-17-activated PCs, but not ECs, induce pertussis toxin-sensitive neutrophil polarization, likely mediated by PC-secreted chemokines, and also stimulate neutrophil production of pro-inflammatory molecules, including TNF, IL-1α, IL-1β, and IL-8. Furthermore, IL-17-activated PCs but not ECs can prolong neutrophil survival by producing G-CSF and GM-CSF, delaying the mitochondria outer membrane permeabilization and caspase 9 activation. Importantly, neutrophils exhibit enhanced phagocytic capacity after activation by CM from IL-17-treated PCs. We conclude that PCs, not ECs, are the major target of IL-17 within the microvessel wall and that IL-17-activated PCs can modulate neutrophil functions within the perivascular tissue space.

show abstract

“…OLR1 may serve various roles in endothelial dysfunction and proinflammatory signaling (20). In addition, IL17 secreted from Th17 cells, may have diverse roles in various inflammatory diseases (11). IL17 has proatherogenic effects, inducing chemokine, cytokine and matrix metalloproteinase production (21).…”

Section: Discussionmentioning

confidence: 99%

“…Mai et al (11) demonstrated that the hyperlipidemia stimulus oxLDL upregulated IL17 receptors in human and mouse primary aortic endothelial cells and that IL17A, in turn, activated human and mouse primary aortic endothelial cells via the upregulation of pro-inflammatory cytokines such as IL6 and granulocyte-macrophage colony-stimulating factor. In another study, atherogenic mice exhibited increased levels of serum IL17 and Th17 cells (22).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Upregulation of OLR1 and IL17A genes and their association with blood glucose and lipid levels in femoropopliteal artery disease

Arslan

Bayoğlu

Tel

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Oxidized low-density lipoprotein receptor 1 (OLR1) and interleukin 17A (IL17A) have pro-inflammatory roles in the development of cardiovascular disorders. The present study evaluated the association of OLR1 and IL17A and their polymorphisms with the development of femoropopliteal (FP) artery disease. The mRNA expression of OLR1 and IL17A in peripheral blood mononuclear cells as well as the frequency of OLR1 rs11053646 and IL17A rs8193037 and rs3819025 polymorphisms were assessed by polymerase chain reaction in 70 patients with FP artery disease and 80 age-matched disease-free controls. Furthermore, the levels of plasma cytokines were assessed by multiplex immunoassay. OLR1 and IL17A mRNA expression was significantly higher in patients with FP artery disease compared with that in controls (P<0.001). No significant difference was observed in the genotypic frequencies of OLR1 rs11053646 (P= 0.87) or in IL17A rs8193037 and rs3819025 (P= 0.80 and 0.92, respectively) polymorphisms between patients with FP artery disease and controls. Plasma IL4, -6, -10, -22, -31 and -33 as well as soluble cluster of differentiation 40 ligand and tumor necrosis factor-α levels were significantly increased among FP artery disease patients compared with controls (P<0.05). Furthermore, OLR1 expression was positively correlated with triglyceride (r= 0.463, P<0.001), low-density lipoprotein cholesterol (r= 0.507, P<0.001) and total cholesterol levels (r= 0.357, P= 0.006) in patients with FP artery disease. To the best of our knowledge, the present study was the first to identify an association between OLR1 and IL17A genes and FP artery disease. OLR1 and IL17A mRNA transcripts may be associated with blood lipid parameters and with the development of FP artery disease.

show abstract

Interleukin-17A Promotes Aortic Endothelial Cell Activation via Transcriptionally and Post-translationally Activating p38 Mitogen-activated Protein Kinase (MAPK) Pathway

Abstract: Interleukin-17 (IL-17)-secreting T helper 17 cells were recently identified as a CD4؉ T helper subset and implicated in various inflammatory and autoimmune diseases.

Cited by 71 publications

References 49 publications

Lysophospholipid Receptors, as Novel Conditional Danger Receptors and Homeostatic Receptors Modulate Inflammation—Novel Paradigm and Therapeutic Potential

Lysophospholipid Receptors, as Novel Conditional Danger Receptors and Homeostatic Receptors Modulate Inflammation—Novel Paradigm and Therapeutic Potential

IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium

Upregulation of OLR1 and IL17A genes and their association with blood glucose and lipid levels in femoropopliteal artery disease

Contact Info

Product

Resources

About