Usage Information
Citation Information: JCI Insight. 2024;9(14):e178525. https://doi.org/10.1172/jci.insight.178525.
Abstract
Neutrophils (polymorphonuclear leukocytes, PMNs) comprise a major component of the immune cell infiltrate during acute mucosal inflammation and have an important role in molding the inflammatory tissue environment. While PMNs are essential to clearance of invading microbes, the major PMN antimicrobial enzyme myeloperoxidase (MPO) can also promote bystander tissue damage. We hypothesized that blocking MPO would attenuate acute colitis and prevent the development of chronic colitis by limiting bystander tissue damage. Using the acute and chronic dextran sodium sulfate model of murine colitis, we demonstrated that MPO-deficient mice experienced less inflammation and more rapidly resolved colitis relative to wild-type controls. Mechanistic studies demonstrated that activated MPO disrupted intestinal epithelial barrier function through the dysregulation of the epithelial tight junction proteins. Our findings revealed that activated MPO chlorinates tyrosine within several tight junction proteins, thereby promoting tight junction mislocalization and dysfunction. These observations in cell models and in murine colitis were validated in human intestinal biopsies from individuals with ulcerative colitis and revealed a strong correlation between disease severity (Mayo score) and tissue chlorinated tyrosine levels. In summary, these findings implicate MPO as a viable therapeutic target to limit bystander tissue damage and preserve mucosal barrier function during inflammation.
Authors
Ian M. Cartwright, Liheng Zhou, Samuel D. Koch, Nichole Welch, Daniel Zakharov, Rosemary Callahan, Calen A. Steiner, Mark E. Gerich, Joseph C. Onyiah, Sean P. Colgan
Usage data is cumulative from July 2024 through March 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,179 | 105 |
| 421 | 32 | |
| Figure | 407 | 1 |
| Table | 43 | 0 |
| Supplemental data | 76 | 1 |
| Citation downloads | 53 | 0 |
| Totals | 2,179 | 139 |
| Total Views | 2,318 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
