Lipopolysaccharide Attenuates Induction of Proallergic Cytokines, Thymic Stromal Lymphopoietin, and Interleukin 33 in Respiratory Epithelial Cells Stimulated with PolyI:C and Human Parechovirus.
Epidemiological studies based on the "hygiene hypothesis" declare that the level of childhood exposure to environmental microbial products is inversely related to the incidence of allergic diseases in later life. Multiple types of immune cell-mediated immune regulation networks support the hygiene hypothesis. Epithelial cells are the first line of response to microbial products in the environment and bridge the innate and adaptive immune systems; however, their role in the hygiene hypothesis is unknown. To demonstrate the hygiene hypothesis in airway epithelial cells, we examined the effect of lipopolysaccharide (LPS; toll-like receptor 4 ligand) on the expression of the proallergic cytokines thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL33) in H292 cells (pulmonary mucoepidermoid carcinoma cells). Stimulation with the TLR ligand polyI:C and human parechovirus type 1 (HPeV1) but not LPS-induced TSLP and IL33 through interferon regulatory factor 3 (IRF3) and NF-κB activity, which was further validated by using inhibitors (dexamethasone and Bay 11-7082) and short hairpin RNA-mediated gene knockdown. Importantly, polyI:C and HPeV1-stimulated TSLP and IL33 induction was reduced by LPS treatment by attenuating TANK-binding kinase 1, IRF3, and NF-κB activation. Interestingly, the basal mRNA levels of TLR signaling proteins were downregulated with long-term LPS treatment of H292 cells, which suggests that such long-term exposure modulates the expression of innate immunity signaling molecules in airway epithelial cells to mitigate the allergic response. In contrast to the effects of LPS treatment, the alarmin high-mobility group protein B1 acts in synergy with polyI:C to promote TSLP and IL33 expression. Our data support part of the hygiene hypothesis in airway epithelia cellsin vitro. In addition to therapeutic targeting of TSLP and IL33, local application of non-pathogenic LPS may be a rational strategy to prevent allergies.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University , Kaohsiung , Taiwan.
Tsang-Hsiung
TH
Lin
Department of Medical Education and Research, Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
Chih-Chi
CC
Cheng
Department of Otorhinolaryngology - Head and Neck Surgery, Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
Hsing-Hao
HH
Su
Department of Family Medicine, Zuoying Branch of Kaohsiung Armed Forces General Hospital , Kaohsiung , Taiwan.
Nan-Chieh
NC
Huang
Department of Pharmacy, Tajen University , Pingtung , Taiwan.
Jih-Jung
JJ
Chen
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology, Center for Menopause and Reproductive Medicine Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Hong-Yo
HY
Kang
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan.
Tsung-Hsien
TH
Chang
HMGB1; IL33; TSLP; hygiene hypothesis; innate immunity