Inflammation is a complex process involving
cytokine production to regulate host defense cascades in order to clear pathogenic agents. Upregulation of inflammatory
cytokines, such as
IL-6 and
IL-8 by bacteria
infection, occurs in pulmonary tissues and has been demonstrated to be critical to the lung inflammatory response.
Glucosamine, primarily identified as an anti-
arthritis supplement, has been also regarded as a potential
anti-inflammatory agent. Thus we hypothesized that
lipopolysaccharide (LPS) would activate
IL-6 and
IL-8 expressions in human primary bronchial epithelial cells and
glucosamine could attenuate such an effect. The RT-PCR, real-time PCR, and ELISA analyses demonstrated that LPS-induced mRNAs encoding
IL-6 and
IL-8 and the subsequent secretion of
IL-6 and
IL-8 were inhibited by
glucosamine treatment. MTT,
alamarBlue, and
annexin V apoptosis assays all suggested that this inhibition effect was not due to a cytotoxic effect mediated by
glucosamine. Using the inhibitors of the MAP
kinases and NFkappaB, it was revealed that p38, JNK and ERK, as well as NFkappaB, are all involved in LPS-induced
IL-8 secretion; however only p38 is involved in LPS-induced
IL-6 secretion. Immunoblot analysis further demonstrated that LPS-mediated phosphorylation of JNK and ERK, but not the LPS-induced NFkappaB translocation, was inhibited by
glucosamine. Altogether, our results indicate that
glucosamine can potently suppress LPS-induced inflammatory
cytokine expression, at least in part via attenuation of MAPK activation.