ELR-negative CXC chemokine CXCL11 (IP-9/I-TAC) facilitates dermal and epidermal maturation during wound repair.

Am J Pathol 2008 Sep 31;173(3):643-52. Epub 2008 Jul 31.

Department of Pathology, University of Pittsburgh and Pittsburgh Veteran's Administration Medical Center, Pittsburgh, Pennsylvania 15261, USA.

In skin wounds, the chemokine CXCR3 receptor appears to play a key role in coordinating the switch from regeneration of the ontogenically distinct mesenchymal and epithelial compartments toward maturation. However, because CXCR3 equivalently binds four different ELR-devoid CXC chemokines (ie, PF4/CXCL4, IP-10/CXCL10, MIG/CXCL9, and IP-9/CXCL11), we sought to identify the ligand that coordinates epidermal coverage with the maturation of the underlying superficial dermis. Because CXCL11 (IP-9 or I-TAC) is produced by redifferentiating keratinocytes late in the regenerative phase when re-epithelialization is completed and matrix maturation ensues, we generated mice in which an antisense construct (IP-9AS) eliminated IP-9 expression during the wound-healing process. Both full and partial thickness excisional wounds were created and analyzed histologically throughout a 2-month period. Wound healing was impaired in the IP-9AS mice, with a hypercellular and immature dermis noted even after 60 days. Re-epithelialization was delayed with a deficient delineating basement membrane persisting in mice expressing the IP-9AS construct. Provisional matrix components persisted in the dermis, and the mature basement membrane components laminin V and collagen IV were severely diminished. Interestingly, the inflammatory response was not diminished despite IP-9/I-TAC being chemotactic for such cells. We conclude that IP-9 is a key ligand in the CXCR3 signaling system for wound repair, promoting re-epithelialization and modulating the maturation of the superficial dermis.

Download full-text PDF

Source
http://dx.doi.org/10.2353/ajpath.2008.070990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527079PMC
September 2008
14 Reads

Publication Analysis

Top Keywords

basement membrane
8
wound repair
8
superficial dermis
8
maturation
5
underlying superficial
4
deficient delineating
4
dermis cxcl11
4
dermis
4
cxcl11 ip-9
4
ip-9 i-tac
4
dermis days
4
redifferentiating keratinocytes
4
immature dermis
4
produced redifferentiating
4
days re-epithelialization
4
re-epithelialization delayed
4
i-tac produced
4
delayed deficient
4
maturation underlying
4
expressing ip-9as
4

Similar Publications