Modulation of expression of the anti-inflammatory cytokines interleukin-13 and interleukin-10 by interleukin-3.

Abstract

Interleukin (IL)-4, IL-10 and IL-13 are cytokines with potent anti-inflammatory activities. Prevention of pathological inflammation at mucosal surfaces appears to be due, in part, to the presence of these cytokines. One potential source for these cytokines is the mast cell which resides at mucosal surfaces. Demonstrated in this report are the findings that bone marrow-derived mucosal-like mast cells constitutively expressed IL-13 whereas bone marrow-derived connective tissue-like mast cells demonstrated IL-13 transcription only after Fc epsilon RI-mediated activation or the addition of exogenous IL-3. A similar pattern of expression of IL-10 by these mast cell types was also evident and matches that of IL-4 previously reported. Intracellular cytokine staining indicated that IL-10 protein is constitutively expressed by the bone marrow-derived mucosal-like mast cells but is only evident in the bone marrow-derived connective tissue-like mast cells after induction with IL-3. The increase of IL-13 and IL-10 transcripts in the connective tissue-like mast cells following IL-3 treatment is not mast cell specific, in that splenic and bone marrow cells also demonstrated the same phenomenon. These data suggest that mucosal mast cells may have a constitutive repertoire of Th2 cytokines with potential anti-inflammatory activity, while connective tissue mast cells may not. However, production of such cytokines can be induced in the connective tissue mast cell and other cell types of the immune response by the addition of IL-3.