Tags

Type your tag names separated by a space and hit enter

Interleukin-32: a new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis.
Hepatology 2011; 53(6):1819-29Hep

Abstract

Interleukin 32 (IL-32) is a recently described proinflammatory cytokine that activates p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), thereby inducing proinflammatory cytokines such as IL-1β and tumor necrosis factor alpha (TNF-α). We investigated the role of IL-32 in patients with chronic hepatitis C virus (HCV) infection. Steady-state hepatic messenger RNA (mRNA) levels of IL-32 were determined in a cohort of 90 subjects; anti-IL-32 staining was used in a second cohort of 132 consecutive untreated chronic HCV patients. Correlations with histological features of steatosis, inflammation, and fibrosis were made. In vitro, endogenous IL-32 in monocytes and in the human hepatoma cell line Huh-7.5 were examined. The effects of IL-32-overexpression and IL-32-silencing on HCV replication were studied using HCV luciferase reporter viruses. There were highly significant positive associations between hepatic IL-32 mRNA expression and liver steatosis, inflammation, fibrosis, smooth muscle actin (SMA) area, and serum alanine aminotransferase (ALT) levels. IL-32 protein expression was positively associated with portal inflammation, SMA area, and ALT. In vitro, IL-1β and TNF-α significantly induced IL-32 expression in human Huh-7.5 cells. Alone, stimulation with interferon alpha (IFN-α) did not induce IL-32 expression in Huh-7.5. However, IFN-α exerted a significant additive effect on TNF-α-induced but not IL-1β-induced IL-32 expression, particularly in CD14+ monocytes. This effect was dependent both on NF-κB and Jak/STAT signaling. Viral infection of Huh-7.5 cells resulted in a significant (11-fold) induction of IL-32 mRNA expression. However, modulation of IL-32 in Huh-7.5 cells by overexpression or silencing did not influence HCV virus replication as determined by luciferase assays.

CONCLUSION

IL-32 is a novel proinflammatory cytokine involved in HCV-associated liver inflammation/fibrosis. IL-32 is expressed by human hepatocytes and hepatoma cells and its expression is regulated by proinflammatory stimuli.

Authors+Show Affiliations

Christian Doppler Research Laboratory for Gut Inflammation, Innsbruck Medical University, Innsbruck, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21381070

Citation

Moschen, Alexander R., et al. "Interleukin-32: a New Proinflammatory Cytokine Involved in Hepatitis C Virus-related Liver Inflammation and Fibrosis." Hepatology (Baltimore, Md.), vol. 53, no. 6, 2011, pp. 1819-29.
Moschen AR, Fritz T, Clouston AD, et al. Interleukin-32: a new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis. Hepatology. 2011;53(6):1819-29.
Moschen, A. R., Fritz, T., Clouston, A. D., Rebhan, I., Bauhofer, O., Barrie, H. D., ... Tilg, H. (2011). Interleukin-32: a new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis. Hepatology (Baltimore, Md.), 53(6), pp. 1819-29. doi:10.1002/hep.24285.
Moschen AR, et al. Interleukin-32: a New Proinflammatory Cytokine Involved in Hepatitis C Virus-related Liver Inflammation and Fibrosis. Hepatology. 2011;53(6):1819-29. PubMed PMID: 21381070.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-32: a new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis. AU - Moschen,Alexander R, AU - Fritz,Teresa, AU - Clouston,Andrew D, AU - Rebhan,Ilka, AU - Bauhofer,Oliver, AU - Barrie,Helen D, AU - Powell,Elizabeth E, AU - Kim,Soo-Hyun, AU - Dinarello,Charles A, AU - Bartenschlager,Ralf, AU - Jonsson,Julie R, AU - Tilg,Herbert, Y1 - 2011/05/14/ PY - 2010/06/20/received PY - 2011/02/23/accepted PY - 2011/3/8/entrez PY - 2011/3/8/pubmed PY - 2011/8/30/medline SP - 1819 EP - 29 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 53 IS - 6 N2 - UNLABELLED: Interleukin 32 (IL-32) is a recently described proinflammatory cytokine that activates p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), thereby inducing proinflammatory cytokines such as IL-1β and tumor necrosis factor alpha (TNF-α). We investigated the role of IL-32 in patients with chronic hepatitis C virus (HCV) infection. Steady-state hepatic messenger RNA (mRNA) levels of IL-32 were determined in a cohort of 90 subjects; anti-IL-32 staining was used in a second cohort of 132 consecutive untreated chronic HCV patients. Correlations with histological features of steatosis, inflammation, and fibrosis were made. In vitro, endogenous IL-32 in monocytes and in the human hepatoma cell line Huh-7.5 were examined. The effects of IL-32-overexpression and IL-32-silencing on HCV replication were studied using HCV luciferase reporter viruses. There were highly significant positive associations between hepatic IL-32 mRNA expression and liver steatosis, inflammation, fibrosis, smooth muscle actin (SMA) area, and serum alanine aminotransferase (ALT) levels. IL-32 protein expression was positively associated with portal inflammation, SMA area, and ALT. In vitro, IL-1β and TNF-α significantly induced IL-32 expression in human Huh-7.5 cells. Alone, stimulation with interferon alpha (IFN-α) did not induce IL-32 expression in Huh-7.5. However, IFN-α exerted a significant additive effect on TNF-α-induced but not IL-1β-induced IL-32 expression, particularly in CD14+ monocytes. This effect was dependent both on NF-κB and Jak/STAT signaling. Viral infection of Huh-7.5 cells resulted in a significant (11-fold) induction of IL-32 mRNA expression. However, modulation of IL-32 in Huh-7.5 cells by overexpression or silencing did not influence HCV virus replication as determined by luciferase assays. CONCLUSION: IL-32 is a novel proinflammatory cytokine involved in HCV-associated liver inflammation/fibrosis. IL-32 is expressed by human hepatocytes and hepatoma cells and its expression is regulated by proinflammatory stimuli. SN - 1527-3350 UR - https://www.unboundmedicine.com/medline/citation/21381070/Interleukin_32:_a_new_proinflammatory_cytokine_involved_in_hepatitis_C_virus_related_liver_inflammation_and_fibrosis_ L2 - https://doi.org/10.1002/hep.24285 DB - PRIME DP - Unbound Medicine ER -