IL-17A synergistically enhances TNFα-induced IL-6 and CCL20 production in 3T3-L1 adipocytes.
Interleukin-17A (IL-17A) is known to induce inflammatory responses and to be involved in the pathogenesis of not only autoimmune diseases, but also several metabolic and infectious diseases. In this study, IL-17A is shown to induce IL-6 expression in 3T3-L1 mature adipocytes. Interestingly, we found that IL-17A synergistically amplified TNFα-induced secretion of IL-6 and upregulation of IL-17RA expression in 3T3-L1 adipocytes. Its synergistic effects on IL-6 production were inhibited by pre-treatment with inhibitors of IκBα and JNK. Furthermore, IL-17A cooperatively enhanced LPS-mediated IL-6 production in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. In addition, IL-17A also enhanced CCL20 production in 3T3-L1 adipocytes stimulated with TNFα or co-cultured with LPS-stimulated RAW macrophages. In high-fat diet-fed mouse epididymal adipose tissues, IL-17RA and RORγt mRNA levels were significantly increased and the serum level of CCL20 was also upregulated. Taken together, these data show that, in adipose tissues, IL-17A contributes to exacerbating insulin resistance-enhancing IL-6 production and promotes the infiltration of Th17 cells in cooperation with TNFα; these findings represent a novel hypothesis for the association between IL-17A-producing cells and type 2 diabetes.
Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, 812-0054, Fukuoka, Japan.
Takanori
T
Shinjo
Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, 812-0054, Fukuoka, Japan.
Misaki
M
Iwashita
Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, 812-0054, Fukuoka, Japan.
Akiko
A
Yamashita
Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, 812-0054, Fukuoka, Japan.
Tomomi
T
Sano
Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, 812-0054, Fukuoka, Japan.
Mitsudai
M
Tsuruta
Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, 812-0054, Fukuoka, Japan.
Hiroaki
H
Matsunaga
Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, 812-0054, Fukuoka, Japan.
Terukazu
T
Sanui
Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, 734-8553, Hiroshima, Japan.
Tomoichiro
T
Asano
Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, 812-0054, Fukuoka, Japan. Electronic address: fusanori@dent.kyushu-u.ac.jp.
Fusanori
F
Nishimura
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D054418:Chemokine CCL20 / Q000276:immunology*; D020381:Interleukin-17 / Q000008:administration & dosage / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D015854:Up-Regulation
C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; D020381:Interleukin-17; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
3T3-L1 adipocyte; CCL20; IL-17A; IL-6; Synergy