Authors: Wan-Jiung Hu
Acute Respiratory Distress Syndrome (ARDS) is a very severe syndrome leading to respiratory failure and subsequent mortality. Sepsis is the leading cause of acute respiratory distress syndrome. Thus, extracellular bacteria play an important role in the pathophysiology of ARDS. Overactivated neutrophils are the major effector cells in ARDS. Thus, extracellular bacteria triggered TH17-like innate immunity with neutrophil activation counts for the etiology of ARDS. Here, I use microarray analysis to describe TH17-like innate immunity related cytokine including TGF-β and IL-6 up-regulation in whole blood of ARDS patients. Innate TH17 related TLR1,2,4,5,8, HSP70, G-CSF, GM-CSF, complements, defensin, PMN chemokines, cathepsins, Fc receptors, NCFs, FOS, JunB, CEBPs, NFkB, and leukotriene B4 are all up-regulated. TGF-β secreting Treg cells play important roles in lung fibrosis. Up-regulation of Treg associated STAT5B and TGF-β with down-regulation of MHC genes, TCR genes, and costimulation molecule CD86 are noted. Key TH17 transcription factors, STAT3 and RORα, are down-regulated. Thus, the full adaptive TH17 helper CD4 T cells may not be successfully triggered. Many fibrosis promoting genes are also up-regulated including MMP8, MMP9, FGF13, TIMP1, TIMP2, PLOD1, P4HB, P4HA1, PDGFC, HMMR, HS2ST1, CHSY1, and CSGALNACT. Failure to induce successful adaptive immunity could also attribute to ARDS pathogenesis. Thus, ARDS is actually a TH17-like and Treg immune disorder.
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