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Title of Journal: Inflammation

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Abbravation: Inflammation

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Springer US

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DOI

10.1007/s10980-011-9577-3

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1573-2576

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A Distinct Regulatory Role of Th17 Cytokines IL17

Authors: Hitomi Fujie Kaijun Niu Michiru Ohba Yoshihisa Tomioka Haruki Kitazawa Kengo Nagashima Takashi Ohrui Muneo Numasaki
Publish Date: 2012/01/05
Volume: 35, Issue: 3, Pages: 1119-1131
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Abstract

Th17 cytokines IL17A and IL17F play a critical role in the activation and recruitment of neutrophils at airway inflammation mainly through the induction of CXC chemokines in the lungs Vascular endothelial cells belong to the category of major CXC chemokineproducing cells However until now the precise role of Th17 cytokines in CXC chemokine secretion in lung microvascular endothelial cells LMVECs has not been fully elucidated In this study we examined the biological effects of Th17 cytokines IL17A and IL17F on CXCL1 CXCL5 and CXCL8 release in LMVECs Both IL17 receptor A IL17RA and IL17RC are expressed on the surface of LMVECs In contrast to IL17F IL17A significantly upregulated CXCL1 mRNA expression and protein release whereas both IL17A and IL17F did not have the ability to induce CXCL5 and CXCL8 secretion in LMVECs IL17A and IL17F displayed positive regulatory effects on IL1βinduced CXCL1 CXCL5 and CXCL8 secretion On the other hand IL17A enhanced the upregulating effect of TNFα on CXCL1 CXCL5 and CXCL8 release whereas IL17F had a negative regulatory effect on TNFαmediated secretion Th2 cytokines IL4 and IL13 showed an inhibitory effect on IL1β plus IL17Ainduced CXCL1 CXCL5 and CXCL8 secretion but displayed a positive regulatory effect on TNFα plus IL17Ainduced secretion These results provide evidence that Th17 cytokines IL17A and IL17F have a distinct regulatory role in CXCL1 CXCL5 and CXCL8 expression in LMVECs stimulated either with IL1β or with TNFα Our findings also suggest that CXC chemokine secretion in LMVECs may be complicatedly regulated by Th17 cytokines Th2 cytokines and macrophageassociated cytokines in pathological conditions such as bronchial asthma

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