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A Distinct Regulatory Role of Th17 Cytokines IL-17A and IL-17F in Chemokine Secretion from Lung Microvascular Endothelial Cells

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Abstract

Th17 cytokines IL-17A and IL-17F 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 chemokine-producing 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 IL-17A and IL-17F on CXCL1, CXCL5, and CXCL8 release in LMVECs. Both IL-17 receptor A (IL-17RA) and IL-17RC are expressed on the surface of LMVECs. In contrast to IL-17F, IL-17A significantly upregulated CXCL1 mRNA expression and protein release, whereas both IL-17A and IL-17F did not have the ability to induce CXCL5 and CXCL8 secretion in LMVECs. IL-17A and IL-17F displayed positive regulatory effects on IL-1β-induced CXCL1, CXCL5, and CXCL8 secretion. On the other hand, IL-17A enhanced the upregulating effect of TNF-α on CXCL1, CXCL5, and CXCL8 release, whereas IL-17F had a negative regulatory effect on TNF-α-mediated secretion. Th2 cytokines IL-4 and IL-13 showed an inhibitory effect on IL-1β plus IL-17A-induced CXCL1, CXCL5, and CXCL8 secretion, but displayed a positive regulatory effect on TNF-α plus IL-17A-induced secretion. These results provide evidence that Th17 cytokines IL-17A and IL-17F have a distinct regulatory role in CXCL1, CXCL5, and CXCL8 expression in LMVECs stimulated either with IL-1β or with TNF-α. Our findings also suggest that CXC chemokine secretion in LMVECs may be complicatedly regulated by Th17 cytokines, Th2 cytokines, and macrophage-associated cytokines in pathological conditions such as bronchial asthma.

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Abbreviations

IL:

Interleukin

TNF:

Tumor necrosis factor

mAb:

Monoclonal antibody

hr:

Hour

mRNA:

Messenger ribonucleic acid

GRO:

Growth-related oncogene

GCP:

Granulocyte chemotactic protein

ENA:

Epithelial cell-derived neutrophil-activating protein

MCP-1:

Monocyte chemotactic protein-1

S.D.:

Standard deviation

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ACKNOWLEDGMENTS

This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (to M.N.). We thank Miss Eri Fujita for her excellent assistance in carrying out this study.

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Authors and Affiliations

  1. Department of Nutrition Physiology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, 350-0295, Japan

    Hitomi Fujie, Michiru Ohba & Muneo Numasaki

  2. Laboratory of Health & Sports Science, Division of Biomedical Engineering for Health & Welfare, Tohoku University Graduate School of Biomedical Engineering, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Kaijun Niu

  3. Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan

    Yoshihisa Tomioka

  4. Food Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiya-machi, Aoba-ku, Sendai, 981-8555, Japan

    Haruki Kitazawa

  5. Laboratory of Biostatistics, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, 350-0295, Japan

    Kengo Nagashima

  6. Division of Geriatric Pharmacology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Takashi Ohrui

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  1. Hitomi Fujie
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  2. Kaijun Niu
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  3. Michiru Ohba
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  8. Muneo Numasaki
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Correspondence to Muneo Numasaki.

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Fujie, H., Niu, K., Ohba, M. et al. A Distinct Regulatory Role of Th17 Cytokines IL-17A and IL-17F in Chemokine Secretion from Lung Microvascular Endothelial Cells. Inflammation 35, 1119–1131 (2012). https://doi.org/10.1007/s10753-011-9419-0

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