Follistatin-related protein/follistatin-like 1 evokes an innate immune response via CD14 and toll-like receptor 4

FEBS Lett. 2012 Feb 17;586(4):319-24. doi: 10.1016/j.febslet.2012.01.010.

Kosaku Murakami ¹, Masao Tanaka, Takashi Usui, Daisuke Kawabata, Aoi Shiomi, Mikiko Iguchi-Hashimoto, Masakazu Shimizu, Naoichiro Yukawa, Hajime Yoshifuji, Takaki Nojima, Koichiro Ohmura, Takao Fujii, Hisanori Umehara, Tsuneyo Mimori

Affiliations

Affiliation

1 Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

PMID: 22265692 DOI: 10.1016/j.febslet.2012.01.010

Abstract

Follistatin-related protein (FRP)/follistatin-like 1 (FSTL1) has multi-specific binding nature especially with TGF-β superfamily proteins, and thereby modulates organ development. However, its function in immune systems remains unclear. Previously, we reported FRP interacts with CD14, which is known to mediate Toll-like Receptor 4 (TLR4) signaling. Here, we investigated whether FRP activates TLR4 signaling. Recombinant FRP induced interleukin 6 or interleukin 8 production from target cells in a CD14- and TLR4-dependent manner. Moreover, similar to lipopolysaccharide (LPS), FRP induced tolerance to the second LPS stimulation. FRP has the function of evoking innate immune responses as one of the endogenous TLR4 agonists.

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