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TNF‐α mediated regulation of myosin light chain 20 phosphorylation in lymphatic muscle

We have shown that mesenteric collecting lymphatic vessels isolated from rats with a high fructose induced metabolic syndrome (MetSyn) exhibit a 50% reduction in force generating capacity and reduced calcium sensitivity. We hypothesized that the elevated level of the inflammatory cytokine TNF‐α associated with MetSyn contributes to the mesenteric lymphatic force reduction. Rat mesenteric lymphatic muscle cells (RMLCs) were cultured in the presence of varying amounts of TNF‐α for 1, 24, and 96 hours, and the basal phosphorylation of myosin light chain 20 (MLC20), an indicator for lymphatic muscle contraction was assessed. We found that chronic TNF‐α (20ng/ml) stimulation significantly reduced phospho‐MLC20 to MLC20 ratio in the basal state at 96 hrs while they were unchanged in 1 and 24 hour treated cells. Furthermore chronic stimulation of RMLCs with lipopolysaccharide recapitulated the results from chronic TNF‐ α exposure. We propose that lymphatic muscle force generation capacity reduced in MetSyn animals is partially due to inflammation‐mediated MLC20 phosphorylation regulation. Our data suggest a potential mechanism whereby elevated endotoxin translocation associated with an increase in TNF‐α contribute to the reduction in force production and calcium sensitivity in mesenteric lymphatic vessels of MetSyn animals. Supported by NIH HL86650 to MM; AHA09POST2280005 to SC.