Signaling pathways leading to the activation of IKK and MAPK by thymosin alpha1.
Thymosin alpha 1 (Talpha1) has therapeutic potential in the treatment of infectious diseases and cancer. However, the exact molecular pathways for Talpha1 action are not fully understood. We found that Talpha1 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. Talpha1 triggers the activation of AP-1 and the phosphorylation of JNK and p38. Inhibition of p38 impairs IL-6 production in response to Talpha1. Further, TRAF6 is involved in the activation of JNK and IRAK4 is involved for the activation of IKK and PKCzeta in a Talpha1-induced system. Loss of IRAK4 largely blocked induction of IL-6. Thus, our studies define early signal events that are critical for the Talpha1-induced immune responses.
Peng
Xiao
X
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.
Zhang
Ping
P
Wang
Xin
X
Chan
Justin
J
Zhu
Mingwei
M
Jiang
Meisheng
M
Tuthill
Cynthia
C
Wan
Yinsheng
Y
Dragoi
Ana Maria
AM
Chu
Wen-Ming
WM
D003713:Dendritic Cells / Q000276:immunology; D004789:Enzyme Activation; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives / Q000502:physiology; D000099221:Protein Kinase C zeta
D051550:I-kappa B Kinase; D018664:Interleukin-12; D020928:Mitogen-Activated Protein Kinases; D011493:Protein Kinase C; D000077596:Thymalfasin; D013947:Thymosin; D000099221:Protein Kinase C zeta