Interferon-γ induces interleukin-6 production by neutrophils via the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway

Autor: Shuhei Yoshida, Shunya Yamada, Kohei Yokose, Haruki Matsumoto, Yuya Fujita, Tomoyuki Asano, Naoki Matsuoka, Jumpei Temmoku, Shuzo Sato, Makiko Yoshiro-Furuya, Hiroshi Watanabe, Kiyoshi Migita
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: BMC Research Notes, Vol 14, Iss 1, Pp 1-7 (2021)
Druh dokumentu: article
ISSN: 1756-0500
DOI: 10.1186/s13104-021-05860-w
Popis: Abstract Objective Interferon-gamma (IFN-γ) is overexpressed in rheumatoid synovium and thought to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study, we examined our hypothesis that IFN-γ activates innate immune cells and upregulates inflammatory cytokines. Peripheral blood neutrophils were stimulated with IFN-γ in the presence or absence of Janus kinase (JAK) inhibitors. Interleukin-6 (IL-6) mRNA and protein expression were analyzed using real-time polymerase chain reaction (PCR) method and enzyme-linked immunosorbent assay. Protein phosphorylation of JAKs or STAT1 was assessed by Western blot using phospho-specific antibodies. Results IFN-γ stimulation induces IL-6 expression in protein and mRNA levels in human neutrophils. Furthermore, IFN-γ stimulation induces JAK1/JAK2 phosphorylation and downstream signal transducer and activator of transcription (STAT) 1 phosphorylation in human neutrophils. Although all JAKi, blocked IFN-γ-induced JAK1.2/STAT1 phosphorylation at higher concentrations (100 nM), baricitinib most efficiently inhibited IFN-γ-induced JAK1.2/STAT1 phosphorylation at lower concentrations (≤ 25 nM). Among these JAKi, baricitinib was the most potent regulator for IFN-γ-induced IL-6 production in human neutrophils. Our data indicate that IFN-γ upregulates IL-6 production via the JAK1/2-STAT1 pathway in human innate immune cells. Furthermore, this IFN-γ-mediated IL-6 induction via JAK/STAT was downregulated by JAKi.
Databáze: Directory of Open Access Journals
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