Interleukin 6 indirectly induces keratinocyte migration.
IL-6-deficient transgenic mice (IL-6 KO) display significantly delayed cutaneous wound healing. To further elucidate the role of IL-6 in skin wound healing, epidermal keratinocyte and dermal fibroblast cells were isolated from neonatal IL-6 KO mice and treated with rmIL-6. It was found that rmIL-6 alone did not significantly modulate the proliferation or migration of cultured IL-6 KO keratinocytes. rmIL-6, however, significantly induced the migration of IL-6 KO keratinocytes (up to 5-fold) when co-cultured with dermal fibroblasts. Culture supernatants from IL-6-treated fibroblasts were also found to induce the migration of keratinocytes to a similar degree. Genomics analysis of treated fibroblasts indicated that rmIL-6 does not induce any known soluble keratinocyte migratory factors. rmIL-6 treatment of fibroblast, however, induced a rapid and sustained phosphorylation of STAT3 protein. These data indicate that IL-6 could influence wound healing by inducing keratinocyte migration through the production of a soluble fibroblast-derived factor, and its activity may be associated with STAT3 activation.
Gallucci
Randle M
RM
The University of Oklahoma Health Sciences Center, College of Pharmacy, Department of Pharmaceutical Sciences, Oklahoma City, Oklahoma 73117, USA. randy-gallucci@ouhsc.edu
Sloan
Dusti K
DK
Heck
Julie M
JM
Murray
Anne R
AR
O'Dell
Sijy J
SJ
D000818:Animals; D002455:Cell Division; D002465:Cell Movement / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology*; D015603:Keratinocytes / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014945:Wound Healing
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases