low ph environmental stress inhibits lps and lta-stimulated proinflammatory cytokine production in rat alveolar macrophages

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ID: 199516
2013
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Abstract
Gastric aspiration increases the risks for developing secondary bacterial pneumonia. Cytokine elaboration through pathogen recognition receptors (PRRs) is an important mechanism in initiating innate immune host response. Effects of low pH stress, a critical component of aspiration pathogenesis, on the PRR pathways were examined, specifically toll-like receptor-2 (TLR2) and TLR4, using isolated rat alveolar macrophages (aMØs). We assessed the ability of aMØs after brief exposure to acidified saline to elaborate proinflammatory cytokines in response to lipopolysaccharide (LPS) and lipoteichoic acid (LTA) stimulation, known ligands of TLR4 and TLR2, respectively. Low pH stress reduced LPS- and LTA-mediated cytokine release (CINC-1, MIP-2, TNF-, MCP-1, and IFN-). LPS and LTA increased intracellular Ca2+ concentrations while Ca2+ chelation by BAPTA decreased LPS- and LTA-mediated cytokine responses. BAPTA blocked the effects of low pH stress on most of LPS-stimulated cytokines but not of LTA-stimulated responses. In vivo mouse model demonstrates suppressed E. coli and S. pneumoniae clearance following acid aspiration. In conclusion, low pH stress inhibits antibacterial cytokine response of aMØs due to impaired TLR2 (MyD88 pathway) and TLR4 signaling (MyD88 and TRIF pathways). The role of Ca2+ in low pH stress-induced signaling is complex but appears to be distinct between LPS- and LTA-mediated responses.
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fernandez2013biomedlow Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Stanley F. Fernandez;Christopher Fung;Jadwiga D. Helinski;Ravi Alluri;Bruce A. Davidson;Paul R. Knight
Journal spectrochimica acta - part a: molecular and biomolecular spectroscopy
Year 2013
DOI
10.1155/2013/742184
URL
http://dx.doi.org/10.1155/2013/742184
Keywords
Medicine

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