Corticotropin-releasing factor augments LPS-induced immune/inflammatory responses in JAWSII cells.

Abstract

The effect of corticotropin-releasing factor (CRF) on gastrointestinal tract inflammation via modulation of the immune system cells such as dendritic cells (DCs) is not known. We investigated the expression of CRF and its receptors CRFR1 and CRFR2 in a colonic DC model (JAWSII cells) in a pro-inflammatory and anti-inflammatory milieu. The mRNA expression of CRF and protein expression of CRFR1 and CRFR2 was assessed, and lipopolysaccharide (LPS) was used to induce the maturation of JAWSII cells. JAWSII cells were divided into four groups: control, CRF, LPS, and LPS + CRF. The levels of secreted cytokines IL-6, IL-4, TNF-α, and MIP-1α were determined, both in JAWSII cells and in the culture supernatant, by qRT-PCR and ELISA. The expression of CRFR1 and CRFR2 in JAWSII cells was accompanied by a low CRF expression. Compared with control group, CRF group did not affect the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and MIP-1α, but LPS treatment significantly increased the expression of these cytokines, indicating maturation of JAWSII cells. CRF further augmented the production of IL-6, TNF-α, and MIP-1α in mature JAWSII cells, with no increase in TNF-α mRNA expression. However, the expression of anti-inflammatory factor IL-4 did not change after LPS treatment. CRF treatment decreased the expression of IL-4 in both mature and immature JAWSII cells. JAWSII cells produce low level of CRF and express CRFR1 and CRFR2 surface receptors. CRF promotes immune/inflammatory responses in mature JAWSII cells when induced by LPS treatment.