Proinflammatory cytokine-induced tight junction remodeling through dynamic self-assembly of claudins
| Autor: | Mattie F. Wolf, Michael Koval, Attila E. Farkas, Michael Fromm, Jeremy K. Benedik, Asma Nusrat, Roland Hilgarth, Charles A. Parkos, Susanne M. Krug, Christopher T. Capaldo |
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| Rok vydání: | 2014 |
| Předmět: |
endocrine system diseases
CHO Cells Biology Proinflammatory cytokine Tight Junctions 03 medical and health sciences Interferon-gamma Mice 0302 clinical medicine Cricetulus Cricetinae Animals Humans Claudin-4 Claudin Molecular Biology Barrier function 030304 developmental biology 0303 health sciences Tight junction Tumor Necrosis Factor-alpha Fluorescence recovery after photobleaching Cell Biology Articles Cell biology Caco-2 Cell Biology of Disease 030220 oncology & carcinogenesis Claudins Tumor necrosis factor alpha Caco-2 Cells Protein Multimerization Intracellular HeLa Cells |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 |
| Popis: | Epithelial barriers are vital components of the innate immune system. This barrier is provided by tight junctions and compromised by proinflammatory cytokine signaling. Study of claudin 4 live-cell protein dynamics shows that tight junctions are self-assembling systems that undergo remodeling through heterotypic claudin incompatibility. Tight junctions (TJs) are dynamic, multiprotein intercellular adhesive contacts that provide a vital barrier function in epithelial tissues. TJs are remodeled during physiological development and pathological mucosal inflammation, and differential expression of the claudin family of TJ proteins determines epithelial barrier properties. However, the molecular mechanisms involved in TJ remodeling are incompletely understood. Using acGFP-claudin 4 as a biosensor of TJ remodeling, we observed increased claudin 4 fluorescence recovery after photobleaching (FRAP) dynamics in response to inflammatory cytokines. Interferon γ and tumor necrosis factor α increased the proportion of mobile claudin 4 in the TJ. Up-regulation of claudin 4 protein rescued these mobility defects and cytokine-induced barrier compromise. Furthermore, claudins 2 and 4 have reciprocal effects on epithelial barrier function, exhibit differential FRAP dynamics, and compete for residency within the TJ. These findings establish a model of TJs as self-assembling systems that undergo remodeling in response to proinflammatory cytokines through a mechanism of heterotypic claudin-binding incompatibility. |
| Databáze: | OpenAIRE |
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