Constitutive expression and regulated release of the transmembrane chemokine CXCL16 in human and murine skin.
The CXC-chemokine ligand 16 (CXCL16) is expressed as a transmembrane adhesion molecule and can be released as a chemoattractant. Both functions are carried out by binding of CXCL16 to its receptor, CXC-chemokine receptor 6 (CXCR6). We here provide early evidence that CXCL16 is expressed in situ by epidermal keratinocytes of normal skin on messenger RNA and protein level and released into the wound exudate upon injury. Cultured human and murine keratinocyte cell lines (HaCaT and PAM212, respectively) as well as primary keratinocyte cultures constitutively express transmembrane CXCL16 on the cell surface. Soluble CXCL16 is released by its limited proteolytic cleavage involving the disintegrin-like metalloproteinase (ADAM)10 but not the closely related ADAM17, as shown by specific inhibitors and small-interfering RNA knockdown experiments. This shedding of CXCL16 is reduced by serum starvation but enhanced by cell stimulation with ionomycin or by UVB irradiation. Soluble CXCL16 from keratinocytes was shown to bind and activate CXCR6, and marked expression of this receptor was found on a subpopulation of T cells in the dermis. Thus, CXCL16 is constitutively expressed on the surface of human epidermal keratinocytes, released upon cell activation or photodamage and may then target CXCR6-expressing T cells in the dermis.
Scholz
Felix
F
Department of Dermatology, Venerology and Allergology, UKSH, Kiel, Germany.
Schulte
Alexander
A
Adamski
Frederic
F
Hundhausen
Christian
C
Mittag
Jens
J
Schwarz
Agatha
A
Kruse
Marie-Luise
ML
Proksch
Ehrhardt
E
Ludwig
Andreas
A
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism*; D020405:Dermis / Q000166:cytology / Q000276:immunology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D034741:RNA, Small Interfering; D051116:Receptors, Scavenger / Q000235:genetics* / Q000378:metabolism*; D012867:Skin / Q000276:immunology* / Q000378:metabolism*; D015595:Skin Aging / Q000276:immunology; D012995:Solubility; D015854:Up-Regulation / Q000276:immunology
C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051116:Receptors, Scavenger; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse