IL-33 Enhanced the Proliferation and Constitutive Production of IL-13 and IL-5 by Fibrocytes

Abstract EN

Interleukin-33 appears to play important roles in the induction of allergic airway inflammation.

However, whether IL-33 is involved in airway remodeling remains unclear.

Because fibrocytes contribute to tissue remodeling in the setting of chronic inflammation, we examined the effects of IL-33 on fibrocyte functions.

Fibrocytes were generated in vitro from peripheral blood mononuclear cells by culturing in the presence of platelet derived growth factors and the cells were stimulated with IL-33.

IL-33 enhanced cell proliferation, α-SMA expression, and pro-MMP-9 activity by the fibrocytes without increasing endogenous transforming growth factor-β1 production.

Fibrocytes constitutively expressed IL-13 and IL-5, and their production was augmented by stimulation with IL-33.

Dexamethasone inhibited the functions of fibrocytes, but IL-33 made fibrocytes slightly refractory to the inhibitory effect of dexamethasone in terms of IL-13 production.

Montelukast suppressed IL-13 production by nonstimulated fibrocytes but not those stimulated by IL-33.

These findings suggest that IL-33 is involved in the airway remodeling process through its modulation of fibrocyte function independent of antigen stimulation.

IL-33 might partially reduce the therapeutic effects of glucocorticoid and cysteinyl leukotriene receptor antagonist on fibrocyte-mediated Th2 responses.