Regulatory mechanisms and their therapeutic implications of interleukin-12 production in immune cells.
Studies with neutralizing anti-interleukin (IL)-12 antibodies and IL-12-deficient mice have suggested that endogenous IL-12 plays an important role in the normal host defense against infection by a variety of intracellular microorganisms. However, IL-12 also appears to play a central role in the pathogenesis of autoimmune diseases such as multiple sclerosis or rheumatic arthritis. Therefore, it is crucial to understand how IL-12 is produced and its production is regulated at the molecular level. IL-12 production is differentially regulated through multiple pathways, which can be classified as follows: nuclear factor-kappaB (NF-kappaB) and other transcription factors, p38 mitogen-activated protein (MAP) kinase, cyclic adenosine monophosphate (cyclic AMP)-modulating molecules, cell membrane ion channels and pumps, nitric oxide (NO), and receptors. In this review we describe the regulatory mechanisms of IL-12 production in immune cells and also some agents to control IL-12 production for the treatment of immune-related diseases.
Kang
Bok Yun
BY
Department of Pharmacy, College of Pharmacy and Research Institute of Drug Development, Chonnam National University, 300 Yongbong-dong, Buk-ku, Gwangju 500-757, South Korea.
Kim
Eugene
E
Kim
Tae Sung
TS
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000627:therapeutic use; D051379:Mice; D015398:Signal Transduction
D018664:Interleukin-12