| First Author | Choi J | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 49 | Pages | 21082-6 |
| PubMed ID | 21078994 | Mgi Jnum | J:167160 |
| Mgi Id | MGI:4867353 | Doi | 10.1073/pnas.1015418107 |
| Citation | Choi J, et al. (2010) Paradoxical effects of constitutive human IL-32{gamma} in transgenic mice during experimental colitis. Proc Natl Acad Sci U S A 107(49):21082-6 |
| abstractText | Inflammatory cytokines mediate inflammatory bowel diseases (IBDs) and cytokine blocking therapies often ameliorate the disease severity. IL-32 affects inflammation by increasing the production of IL-1, TNFalpha, and several chemokines. Here, we investigated the role of IL-32 in intestinal inflammation by generating a transgenic (TG) mouse expressing human IL-32gamma (IL-32gamma TG). Although IL-32gamma TG mice are healthy, constitutive serum and colonic tissue levels of TNFalpha are elevated. Compared with wild-type (WT) mice, IL-32gamma TG mice exhibited a modestly exacerbated acute inflammation early following the initiation of dextran sodium sulfate (DSS)-induced colitis. However, after 6 d, there was less colonic inflammation, reduced tissue loss, and improved survival rate compared with WT mice. Associated with attenuated tissue damage, colonic levels of TNFalpha and IL-6 were significantly reduced in the IL-32gamma TG mice whereas IL-10 was elevated. Cultured colon explants from IL-32gamma TG mice secreted higher levels of IL-10 compared with WT mice and lower levels of TNFalpha and IL-6. Constitutive levels of IL-32gamma itself in colonic tissues were significantly lower following DSS colitis. Although the highest level of serum IL-32gamma occurred on day 3 of colitis, IL-32 was below constitutive levels on day 9. The ability of IL-32gamma to increase constitutive IL-10 likely reduces TNFalpha, IL-6, and IL-32 itself accounting for less inflammation. In humans with ulcerative colitis (UC), serum IL-32 is elevated and colonic biopsies contain IL-32 in inflamed tissues but not in uninvolved tissues. Thus IL-32gamma emerges as an example of how innate inflammation worsens as well as protects intestinal integrity. |
