Toll-like receptor 2 is overexpressed in Familial Mediterranean fever patients and is inhibited by colchicine treatment

Hava Ben-David, Avi Livneh, Merav Lidar, Olga Feld, Souad Haj Yahia, Chagai Grossman, Ilan Ben-Zvi*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations

Abstract

Aim: To study the role of Toll-like receptor (TLR) 2 in Familial Mediterranean fever (FMF) inflammatory process. Methods: TLR2 expression on monocytes of FMF attack-free patients (n = 20) and the effect of sera of FMF patients with an acute attack (n = 9) on TLR2 expression on monocytes of healthy donors were studied by flow cytometry (FACS). TLR2 expression was also studied in THP-1 cells, and TLR2 downstream signaling was studied by ELISA for the secretion of IL-1β and pro-inflammatory cytokines or by western blotting to measure nuclear factor (NF)-κB. Results: FMF attack-free patients had increased CD14 + TLR2+ cell count as compared to healthy donors. High-dose colchicine treatment (≥2 mg/d) inhibited this increased expression in FMF patients. Colchicine in vitro also inhibited TLR2 expression on THP-1 cells. Sera from FMF patients with an acute attack induced TLR2 expression by both monocytes of healthy donors and THP-1 cells as well as pro-inflammatory cytokine secretion by healthy monocytes, while colchicine inhibited this induction. Pam2CSK4 increased interleukin-1β (IL-1β) secretion by peripheral blood mononuclear cells (PBMCs) of healthy donors, and this activation was inhibited by colchicine. THP-1 cells presented elevated NF-κB expression when cultured with Pam2CSK4, whereas colchicine inhibited this elevation. Conclusions: TLR2 activation was upregulated in monocytes of FMF patients, and colchicine inhibited this upregulation both in -vitro and in -vivo. This indicates that elevated expression of TLR2 promotes the production of pro-inflammatory cytokines, which may contribute to uncontrolled inflammation in FMF.

Original languageEnglish
Pages (from-to)651-661
Number of pages11
JournalBest Practice and Research: Clinical Rheumatology
Volume32
Issue number5
DOIs
StatePublished - Oct 2018

Funding

FundersFunder number
Israel Science Foundation0202/12

    Keywords

    • FMF
    • IL-1β
    • TLR

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