The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality
Open accessAbstract
Acute lung injury (ALI) is an inflammatory disease with a high mortality rate. Although typically seen in individuals with sepsis, ALI is also a major complication in severe acute pancreatitis (SAP). The pathophysiology of SAP-associated ALI is poorly understood, but elevated serum levels of IL-6 is a reliable marker for disease severity. Here, we used a mouse model of acute pancreatitis-associated (AP-associated) ALI to determine the role of IL-6 in ALI lethality. Il6-deficient mice had a lower death rate compared with wild-type mice with AP, while mice injected with IL-6 were more likely to develop lethal ALI. We found that inflammation-associated NF-κB induced myeloid cell secretion of IL-6, and the effects of secreted IL-6 were mediated by complexation with soluble IL-6 receptor, a process known as trans-signaling. IL-6 trans-signaling stimulated phosphorylation of STAT3 and production of the neutrophil attractant CXCL1 in pancreatic acinar cells. Examination of human samples revealed expression of IL-6 in combination with soluble IL-6 receptor was a reliable predictor of ALI in SAP. These results demonstrate that IL-6 trans-signaling is an essential mediator of ALI in SAP across species and suggest that therapeutic inhibition of IL-6 may prevent SAP-associated ALI.
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Cites
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Self-citationTargeting IL-6 trans-signalling: past, present and future prospects
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Self-citationBlockade of IL-6 Trans Signaling Attenuates Pulmonary Fibrosis
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Interleukin-6: from basic biology to selective blockade of pro-inflammatory activities
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Metadata
- Authors
- Zhang, H., Neuhöfer, P., Song, L., Rabe, B., Lesina, M., Kurkowski, M. U., Treiber, M., Wartmann, T., Regnér, S., Thorlacius, H., Saur, D., Weirich, G., Yoshimura, A., Halangk, W., Mizgerd, J. P., Schmid, R. M., Rose-John, S., & Algül, H.
- Venue
- Journal of Clinical Investigation
- Published
- 2013-02-15
- Volume
- 123
- Issue
- 3
- Pages
- 1019-1031
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2011400811
- Cited by
- 288
- References
- 50
- FWCI
- 20.36
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhang, H., Neuhöfer, P., Song, L., Rabe, B., Lesina, M., Kurkowski, M. U., Treiber, M., Wartmann, T., Regnér, S., Thorlacius, H., Saur, D., Weirich, G., Yoshimura, A., Halangk, W., Mizgerd, J. P., Schmid, R. M., Rose-John, S., & Algül, H. (2013). IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality. Journal of Clinical Investigation. https://doi.org/10.1172/jci64931
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