HSP60 activity on human bronchial epithelial cells. (December 2017)

• Record Type: Journal Article
• Authors: Sangiorgi, Claudia; Vallese, Davide; Gnemmi, Isabella; Bucchieri, Fabio; Balbi, Bruno; Brun, Paola; Leone, Angelo; Giordano, Andrea; Conway de Macario, Everly; Macario, Alberto JL; Cappello, Francesco; Di Stefano, Antonino
• Is Part Of: International journal of immunopathology and pharmacology. Volume 30:Number 4(2017)
• Page Start: 333
• Page End: 340
• Publication Date: 2017-12
• Subjects: COPD -- CREB1 -- ERK1 -- HSP60 -- IL-8 -- IL-10 -- JNK1 -- MyD88 -- NF-κB p65 subunit -- p38α -- TLR-4 -- 16-HBE; Immunopathology -- Periodicals; Pharmacology -- Periodicals; Inflammation -- Periodicals; 615.1
• DOI: 10.1177/0394632017734479
• Languages: English
• ISSNs: 0394-6320

Abstract

HSP60 has been implicated in chronic inflammatory disease pathogenesis, including chronic obstructive pulmonary disease (COPD), but the mechanisms by which this chaperonin would act are poorly understood. A number of studies suggest a role for extracellular HSP60, since it can be secreted from cells and bind Toll-like receptors; however, the effects of this stimulation have never been extensively studied. We investigated the effects (pro- or anti-inflammatory) of HSP60 in human bronchial epithelial cells (16-HBE) alone and in comparison with oxidative, inflammatory, or bacterial challenges. 16-HBE cells were cultured for 1–4 h in the absence or presence of HSP60, H2 O2, lipopolysaccharide (LPS), or cytomix. The cell response was evaluated by measuring the expression of IL-8 and IL-10, respectively, pro- and anti-inflammatory cytokines involved in COPD pathogenesis, as well as of pertinent TLR-4 pathway mediators. Stimulation with HSP60 up-regulated IL-8 at mRNA and protein levels and down-regulated IL-10 mRNA and protein. Likewise, CREB1 mRNA was up-regulated. H2 O2 and LPS up-regulated IL-8. Experiments with an inhibitor for p38 showed that this mitogen-activated protein kinase could be involved in the HSP60-mediated pro-inflammatory effects. HSP60 showed pro-inflammatory properties in bronchial epithelial cells mediated by activation of TLR-4-related molecules. The results should prompt further studies on more complex ex-vivo or in-vivo models with the aim to elucidate further the role of those molecules in the pathogenesis of COPD.