Inflammation is a biological response of the immune system that can be triggered by a variety of factors, including pathogens, damaged cells and toxic compounds. These factors may induce acute and/or chronic inflammatory responses in the heart, pancreas, liver, kidney, lung, brain, intestinal tract and reproductive system, potentially leading to tissue damage or disease. Both infectious and non-infectious agents and cell damage activate inflammatory cells and trigger inflammatory signaling pathways, most commonly the NF-κB, MAPK, and JAK-STAT pathways. Here, we review inflammatory responses within organs, focusing on the etiology of inflammation, inflammatory response mechanisms, resolution of inflammation, and organ-specific inflammatory responses.

Summary Many viruses induce hepatitis in humans, highlighting the need to understand the underlying mechanisms of virus-induced liver pathology. The murine coronavirus, mouse hepatitis virus (MHV), causes acute hepatitis in its natural host and provides a useful model for understanding virus interaction with liver cells. The MHV accessory protein, ns2, antagonizes the type I interferon response and promotes hepatitis. We show that ns2 has 2′,5′-phosphodiesterase activity, which blocks the interferon inducible 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway to facilitate hepatitis development. Ns2 cleaves 2′,5′-oligoadenylate, the product of OAS, to prevent activation of the cellular endoribonuclease RNase L and consequently block viral RNA degradation. An ns2 mutant virus was unable to replicate in the liver or induce hepatitis in wild-type mice, but was highly pathogenic in RNase L deficient mice. Thus, RNase L is a critical cellular factor for protection against viral infection of the liver and the resulting hepatitis.

Abstract-The renin-angiotensin system is a major regulator of body sodium, predominantly through the actions of intrarenal angiotensin II of unclear origin. We show that polarized epithelium of the proximal tubule synthesizes and secretes angiotensinogen at its apical side and that the protein can be detected in urine as a function of dietary sodium. Furthermore, we demonstrate that renin is expressed and secreted in a restricted nephron segment, the connecting tubule, also in a sodium-dependent fashion. A paracrine renin-angiotensin system operating along the entire nephron may contribute to long-term arterial pressure regulation by integrating distant tubular sodium-reabsorbing functions.(Hypertension. 1999;34:1265-1274.)

We have used gene targeting to generate relaxin (rlx)-deficient mice. The majority (15 of 17) of homozygous (rlx Ϫ/Ϫ ) mice are fertile and produce normal litters. However their mammary development is deficient; pups are unable to suckle and die within 24 h of birth unless cross-fostered to a wild-type (rlx ϩ/ϩ ) foster mother. [445][446][447][448][449][450][451][452][453] 1999) R ELAXIN was the name given to a factor that was first shown to cause relaxation and softening of the pubic ligaments of the guinea pig (1). Later, this factor was shown to soften the uterine cervix, inhibit myometrial contraction, and increase the length of the interpubic ligament in estrogen-treated ovariectomized mice and/or rats (2).For many years, there were no pure preparations to establish tests for bioactivity and no sensitive homologous assays for measuring changes in plasma relaxin concentrations during pregnancy. When heterologous or homologous assays did become available for some species, it became clear that the patterns of relaxin secretion differed markedly between species. In the rat and mouse, the relaxin concentration is elevated only during the last half of pregnancy (3), whereas the human circulating concentrations of relaxin rise to a peak toward the end of the first trimester, then decrease to a plateau that is maintained for the rest of pregnancy (4).The molecular structure of relaxin is known for many species, and several important points have emerged (5). The relaxins of all species in which it exists are peptides of between 43-64 amino acids, containing two chains, A and B, covalently linked by two disulfide bonds (the C peptide is trimmed off in the processing of prorelaxin to produce relaxin). There is remarkable heterogeneity in the relaxin family, with, in general, no more than 50% structural homology between relaxins of various species (5). Some ruminants (sheep and cow) do not express a functional relaxin gene (6, 7); however they do express a relaxin-like factor (Leydig cell insulin-like peptide) in ovarian cells.In mice and rats, the corpus luteum is the major source of circulating relaxin during pregnancy (8, 9); however, relaxin expression has also been detected in several other tissues. In the rat, moderate levels of relaxin messenger RNA (mRNA) and protein have been detected in the uterus (10, 11), and relaxin gene expression has also been observed in the brain and prostate gland (10, 12). Binding sites for relaxin have been identified in tissues of the reproductive tract, such as the uterus (13), cervix (14, 15), mammary gland, and nipple (15, 16) as well as in the pubic symphysis (17), cardiac atrium, and brain (13,18,19). In the mammary gland the binding sites are located in the epithelial cells of the lobulo-alveolar elements as well as in smooth muscle and in epithelial cells of the skin of the nipple (15,20).The biological actions of relaxin in the pregnant rat have been characterized extensively. They include inhibition of myometrial contraction and connective tissue remodeling at ...