Bcl-3 acts as an innate immune modulator by controlling antimicrobial responses in keratinocytes.

Autor: Büchau AS; Division of Dermatology, Department of Medicine, University of California, San Diego, VA San Diego Healthcare System, San Diego, California 92161, USA., MacLeod DT, Morizane S, Kotol PF, Hata T, Gallo RL
Jazyk: angličtina
Zdroj: The Journal of investigative dermatology [J Invest Dermatol] 2009 Sep; Vol. 129 (9), pp. 2148-55. Date of Electronic Publication: 2009 Mar 12.
DOI: 10.1038/jid.2009.49
Abstrakt: Innate immune responses involve the production of antimicrobial peptides (AMPs), chemokines, and cytokines. We report here the identification of B-cell leukemia (Bcl)-3 as a modulator of innate immune signaling in keratinocytes. In this study, it is shown that Bcl-3 is inducible by the Th2 cytokines IL-4 and IL-13 and is overexpressed in lesional skin of atopic dermatitis (AD) patients. Bcl-3 was shown to be important to cutaneous innate immune responses as silencing of Bcl-3 by small-interfering RNA (siRNA) reversed the downregulatory effect of IL-4 on the HBD3 expression. Bcl-3 silencing enhanced vitamin D3 (1,25D3)-induced gene expression of cathelicidin AMP in keratinocytes, suggesting a negative regulatory function on cathelicidin transcription. Furthermore, 1,25D3 suppressed Bcl-3 expression in vitro and in vivo. This study identified Bcl-3 as an important modulator of cutaneous innate immune responses and its possible therapeutic role in AD.
Databáze: MEDLINE