Endogenous regulation of the acute inflammatory response.
The acute inflammatory response has been triggered in rat lungs by deposition of IgG immune complexes. The inflammatory reaction triggered is highly tissue damaging and requires activation of NF-kappaB with ensuing generation of chemokines and cytokines. Endogenous generation of IL- 10 and IL- 13 as well as secretory leukocyte protease inhibitor (SLPI), significantly regulates this inflammatory response. IL-10 and IL-13 attenuate NF-kappaB activation by interfering with breakdown of IkappaBalpha, while SLPI likewise suppresses NF-kappaB activation, but by interfering with breakdown of IkappaBbeta. Antibody induced blockade of IL-10, IL-13 or SLPI enhances NF-KB activation in lung and exacerbates the lung inflammatory response and injury. These data indicate that endogenous IL-10, IL-13 and SLPI are important regulators of the inflammatory response by reducing gene activation with resultant generation of peptide mediators/cytokines and chemokines.
Ward
Peter A
PA
Department of Pathology, University of Michigan, Ann Arbor 48109, USA. pward@umich.edu
Lentsch
Alex B
AB
D000208:Acute Disease; D000818:Animals; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000378:metabolism; D051381:Rats; D053481:Secretory Leukocyte Peptidase Inhibitor
D018793:Interleukin-13; D016328:NF-kappa B; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D053481:Secretory Leukocyte Peptidase Inhibitor; C506816:Slpi protein, rat; D016753:Interleukin-10