Constitutive expression and regulated release of the transmembrane chemokine CXCL16 in human and murine skin
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Constitutive expression and regulated release of the transmembrane chemokine CXCL16 in human and murine skin. / Scholz, Felix; Schulte, Alexander; Adamski, Frederic; Hundhausen, Christian; Mittag, Jens; Schwarz, Agatha; Kruse, Marie-Luise; Proksch, Ehrhardt; Ludwig, Andreas.
In: J INVEST DERMATOL, Vol. 127, No. 6, 01.06.2007, p. 1444-55.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Constitutive expression and regulated release of the transmembrane chemokine CXCL16 in human and murine skin
AU - Scholz, Felix
AU - Schulte, Alexander
AU - Adamski, Frederic
AU - Hundhausen, Christian
AU - Mittag, Jens
AU - Schwarz, Agatha
AU - Kruse, Marie-Luise
AU - Proksch, Ehrhardt
AU - Ludwig, Andreas
PY - 2007/6/1
Y1 - 2007/6/1
N2 - 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.
AB - 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.
KW - ADAM Proteins
KW - Amyloid Precursor Protein Secretases
KW - Animals
KW - Cell Adhesion
KW - Cell Line
KW - Chemokines, CXC
KW - Dermis
KW - Epidermis
KW - Gene Expression
KW - Humans
KW - Keratinocytes
KW - Kidney
KW - Membrane Proteins
KW - Mice
KW - Mice, Hairless
KW - RNA, Small Interfering
KW - Receptors, Scavenger
KW - Skin
KW - Skin Aging
KW - Solubility
KW - Up-Regulation
U2 - 10.1038/sj.jid.5700751
DO - 10.1038/sj.jid.5700751
M3 - SCORING: Journal article
C2 - 17363916
VL - 127
SP - 1444
EP - 1455
JO - J INVEST DERMATOL
JF - J INVEST DERMATOL
SN - 0022-202X
IS - 6
ER -