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Chronic Inflammation Deactivated the MAPK pathway and Decreased the TRPV1 Protein Expression in the 50B11 Dorsal Root Ganglion Cell Line
Author(s) -
WANG HANJUN,
Rozanski George J.,
Zucker Irving H.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.697.1
Subject(s) - mapk/erk pathway , trpv1 , dorsal root ganglion , phosphorylation , inflammation , medicine , endocrinology , protein kinase a , tumor necrosis factor alpha , transient receptor potential channel , receptor , chemistry , microbiology and biotechnology , biology , anatomy , dorsum
It has been shown that skeletal muscle metabolic afferents are desensitized in the chronic heart failure (CHF) state, which is associated with a decreased transient receptor potential vanilloid 1 (TRPV1) receptor expression in the lumbar dorsal root ganglia (DRG). However, the molecular mechanisms underlying the downregulated TRPV1 protein expression in lumbar DRG neurons in CHF remain unclear. Because CHF is associated with chronic inflammation, we decided to investigate the potential effects of acute and chronic inflammation on TRPV1 protein expression in the 50B11 DRG Cell line. We used tumor necrosis factor (TNF) alpha (a pro‐inflammatory cytokine) to create an inflammatory environment. Since evidence suggests that the mitogen‐activated protein kinases (MAPK) pathway is involved in the regulation of TRPV1 channel function, we first investigated the time and dose‐dependent effects of TNF alpha on the phosphorylation of ERK (one of the MAPK components). Our time‐course experiments showed that TNF alpha (100 ng/ml) caused peak phosphorylation of ERK at 15 min and lasted up to 3 hours. TNF alpha also dose‐dependently (0.01, 0.1, 1, 10 and 100ng/ml) increased the phosphorylation of ERK with a peak effect at 10 ng/ml (1.6±0.26 at 10 ng/ml and 1.7±0.26 at 100ng/ml vs. Vehicle (1.0±0), n=6, p<0.01) at 15 min. However, either 20‐hour or 5‐day of continuous treatment with TNF alpha decreased the phosphorylation of ERK by 30% compared to vehicle treatment. Furthermore, a 20‐hour treatment with TNF alpha (100 ng/ml) decreased protein expression of TRPV1 by 30% whereas a 5‐day continuous TNF alpha treatment (10 ng/ml) further decreased TRPV1 protein expression by ~90% (0.10±0.04 vs. Vehicle (1.0±0.0), n=8, p<0.01). These data suggest that chronic inflammation causes a significant reduction in TRPV1 protein expression in DRG neurons which is associated with decreased phosphorylation of ERK. Ongoing experiments will determine if the decreased phosphorylation of ERK by chronic treatment with TNF alpha contributes to the loss of TRPV1 receptors in DRG neurons. Support or Funding Information This work was supported by by grants from the National Heart, Lung, and Blood Institute ( 1R01HL121012‐01A1 and R01 HL116608‐01A1).