S100A4 is secreted by airway smooth muscle tissues and activates inflammatory signaling pathways via receptors for advanced glycation end products.

S100A4 is a low-molecular-mass (12 kDa) EF-hand Ca²⁺-binding S100 protein that is expressed in a broad range of normal tissue and cell types. S100A4 can be secreted from some cells to act in an autocrine or paracrine fashion on target cells and tissues. S100A4 has been reported in the extracellular fluids of subjects with several inflammatory diseases, including asthma. Airway smooth muscle plays a critical role in airway inflammation by synthesizing and secreting inflammatory cytokines. We hypothesized that S100A4 may play an immunomodulatory role in airway smooth muscle. Trachealis smooth muscle tissues were stimulated with recombinant His-S100A4, and the effects on inflammatory responses were evaluated. S100A4 induced the activation of Akt and NF-κB and stimulated eotaxin secretion. It also increased the expression of and endogenous S100A4 in airway tissues. Stimulation of airway smooth muscle tissues with IL-13 or TNF-α induced the secretion of S100A4 from the tissues and promoted the expression of endogenous receptors for advanced glycation end products and S100A4. The role of duanyu1648 in mediating the responses to S100A4A was evaluated by expressing a mutant nonfunctional duanyu1648 in tracheal muscle tissues and by treating tissues with a duanyu1648 inhibitor. S100A4 did not activate NF-κB or Akt in tissues that were expressing or treated with a duanyu1648 inhibitor, indicating that S100A4 mediates its effects by acting on Our results demonstrate that inflammatory mediators stimulate the synthesis and secretion of S100A4 in airway smooth muscle tissues and that extracellular S100A4 acts via duanyu1648 to mediate airway smooth muscle inflammation.

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