Differences in wound healing in mice with deficiency of IL-6 versus IL-6 receptor
| Autor: | Andrew M. Paluch, Carol A. Mercer, Premkumar Vummidi Giridhar, Angela F. Drew, Mingfu Zhou, Sara C. Kozma, Holly M. Funk, Molly M. McFarland-Mancini |
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| Rok vydání: | 2010 |
| Předmět: |
MAPK/ERK pathway
Genotype Immunology Blotting Western Inflammation Enzyme-Linked Immunosorbent Assay Fibrin Mice Immune system medicine Immunology and Allergy Animals Receptor Skin Mice Knockout Wound Healing biology Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction MEK inhibitor Immunohistochemistry Receptors Interleukin-6 Mice Inbred C57BL Blotting Southern Interleukin-6 receptor biology.protein medicine.symptom Wound healing Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 184(12) |
| ISSN: | 1550-6606 |
| Popis: | IL-6 modulates immune responses and is essential for timely wound healing. As the functions mediated by IL-6 require binding to its specific receptor, IL-6Rα, it was expected that mice lacking IL-6Rα would have the same phenotype as IL-6–deficient mice. However, although IL-6Rα–deficient mice share many of the inflammatory deficits seen in IL-6–deficient mice, they do not display the delay in wound healing. Surprisingly, mice with a combined deficit of IL-6 and IL-6Rα, or IL-6–deficient mice treated with an IL-6Rα–blocking Ab, showed improved wound healing relative to mice with IL-6 deficiency, indicating that the absence of the receptor contributed to the restoration of timely wound healing, rather than promiscuity of IL-6 with an alternate receptor. Wounds in mice lacking IL-6 showed delays in macrophage infiltration, fibrin clearance, and wound contraction that were not seen in mice lacking IL-6Rα alone and were greatly reduced in mice with a combined deficit of IL-6 and IL-6Rα. MAPK activation-loop phosphorylation was elevated in wounds of IL-6Rα–deficient mice, and treatment of wounds in these mice with the MEK inhibitor U0126 resulted in a delay in wound healing suggesting that aberrant ERK activation may contribute to improved healing. These findings underscore a deeper complexity for IL-6Rα function in inflammation than has been recognized previously. |
| Databáze: | OpenAIRE |
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