Differences in wound healing in mice with deficiency of IL-6 versus IL-6 receptor.
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-6Ralpha, it was expected that mice lacking IL-6Ralpha would have the same phenotype as IL-6-deficient mice. However, although IL-6Ralpha-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-6Ralpha, or IL-6-deficient mice treated with an IL-6Ralpha-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-6Ralpha alone and were greatly reduced in mice with a combined deficit of IL-6 and IL-6Ralpha. MAPK activation-loop phosphorylation was elevated in wounds of IL-6Ralpha-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-6Ralpha function in inflammation than has been recognized previously.
McFarland-Mancini
Molly M
MM
Department of Cancer and Cell Biology, Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, OH 45267, USA.
Funk
Holly M
HM
Paluch
Andrew M
AM
Zhou
Mingfu
M
Giridhar
Premkumar Vummidi
PV
Mercer
Carol A
CA
Kozma
Sara C
SC
Drew
Angela F
AF
D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000172:deficiency* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019947:Receptors, Interleukin-6 / Q000172:deficiency* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D012867:Skin / Q000293:injuries / Q000378:metabolism; D014945:Wound Healing / Q000276:immunology*
D015850:Interleukin-6; D019947:Receptors, Interleukin-6