Injury of skeletal muscle and specific cytokines induce the expression of gap junction channels in mouse dendritic cells

Corvalan, LA; Araya, R; Branes, MC; Sáez PJ; Kalergis, AM; Tobar, JA; Theis, M; Willecke K.; Sáez JC

Abstract

Dendritic cells (DCs) in culture express at least connexin43, a protein subunit of gap junctions, and form gap junction channels, which could be important for T-cells activation. Here, we evaluated whether DCs express connexins in vivo and also to identify components of their microenvironment that regulate the functional expression of gap junctions. In vivo studies were performed in lymph nodes of mice under control conditions or after skeletal muscle damage. In double immunolabeling studies, connexin45 was frequently detected in DEC205+ DCs in lymph nodes of control animals, whereas connexin43 was rarely found in DCs. However, connexin43 was upregulated in DCs after skeletal muscle damage. Upregulation of connexin43 gene expression by tissue damage was also confirmed in mice carrying a β-galactosidase reporter gene in a connexin43 allele. The effect of several cytokines on the expression of functional gap junctions between cultured DCs was also tested. Under control conditions, cultured DCs did not communicate via gap junctions. However, after treatment with keratinocyte-conditioned medium or cytokine mixtures containing at least TNF-α and IL-1α, they became transiently coupled through a pathway sensitive to octanol, a gap junction blocker. Cellular coupling induced by effective cytokine mixtures was prevented by IL-6. Single cytokines (TNF-α, IL-1β, IFN-γ, or IL-6) or other mixtures than the described above did not induce coupling via gap junctions. Increased levels of connexin43 and connexin45 protein and mRNA accompanied the appearance of cellular coupling. These studies provide demonstration of connexin expression and regulation by specific danger signals in DCs. © 2007 Wiley-Liss, Inc.

Más información

Título según WOS: Injury of skeletal muscle and specific cytokines induce the expression of gap junction channels in mouse dendritic cells
Título según SCOPUS: Injury of skeletal muscle and specific cytokines induce the expression of gap junction channels in mouse dendritic cells
Título de la Revista: JOURNAL OF CELLULAR PHYSIOLOGY
Volumen: 211
Número: 3
Editorial: Wiley
Fecha de publicación: 2007
Página de inicio: 649
Página final: 660
Idioma: English
URL: http://doi.wiley.com/10.1002/jcp.20971
DOI:

10.1002/jcp.20971

Notas: ISI, SCOPUS