Signaling Pathways Leading to the Activation of IKK and MAPK by Thymosin α1

Abstract : Thymosin alpha 1 (Tα1) has therapeutic potential in the treatment of infectious diseases and cancer. However, the exact molecular pathways for Tα1 action are not fully understood. We found that Tα1 induces the production of interleukin‐6 (IL‐6), IL‐10, and IL‐12 in murine bone marrow‐derived macrophages (BMDMs) through IKK and MAPK pathways. Tα1 triggers the activation of AP‐1 and the phosphorylation of JNK and p38. Inhibition of p38 impairs IL‐6 production in response to Tα1. Further, TRAF6 is involved in the activation of JNK and IRAK4 is involved for the activation of IKK and PKCζ in a Tα1‐induced system. Loss of IRAK4 largely blocked induction of IL‐6. Thus, our studies define early signal events that are critical for the Tα1‐induced immune responses.