Pathophysiology of interleukin-1 receptor-associated kinase-M: implications in refractory state.
OBJECTIVE
The pseudo-kinase interleukin-1 receptor-associated kinase-M has emerged as a critical molecule in the down-regulation of inflammatory responses. Dysregulation of the toll-like receptor-interleukin-1 receptor-associated kinase system, and in particular interleukin-1 receptor-associated kinase-M up-regulation, are associated with a number of pathologies. This review highlights recent findings on interleukin-1 receptor-associated kinase-M reported in biomedical literature.


RESULTS
Interleukin-1 receptor-associated kinase-M plays a critical role in generating a refractory state of the immune system following monocytes/macrophages encounter with bacteria or tumor cells. This state has been demonstrated so far in patients who suffer from sepsis, leukemia, and acute coronary syndrome, and seems to be associated with interleukin-1 receptor-associated kinase-M overexpression in their circulating monocytes. In addition, the pseudo-kinase represents a central regulator of osteoclast differentiation and activation, and might thus be related to the onset of osteoporosis.


CONCLUSIONS
Interleukin-1 receptor-associated kinase-M is involved in the control of endotoxin tolerance in monocytes, in osteoporosis, as well as in the deactivation of tumor-infiltrating macrophages. Additionally, patients who suffer from several pathologies related to inflammatory responses express high levels of this molecule in their circulating monocytes. Human monocytes treated with a nitric oxide donor also express large amounts of interleukin-1 receptor-associated kinase-M, apparently under the control of tumor necrosis factor-alpha. This mechanism could explain the induction of interleukin-1 receptor-associated kinase-M in monocytes from patients who suffer from an inflammatory pathology.
López-Collazo
Eduardo
E
Research Unit, La Paz Hospital, Madrid, Spain. elopezc.hulp@salud.madrid.org
Fuentes-Prior
Pablo
P
Arnalich
Francisco
F
del Fresno
Carlos
C
D000818:Animals; D003327:Coronary Disease / Q000201:enzymology*; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008958:Models, Molecular; D009369:Neoplasms / Q000201:enzymology*; D010024:Osteoporosis / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D018805:Sepsis / Q000201:enzymology*; D051193:Toll-Like Receptors / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D051193:Toll-Like Receptors; D053592:Interleukin-1 Receptor-Associated Kinases; D017346:Protein Serine-Threonine Kinases