The CXCR3 Activating Chemokines IP-10, Mig, and IP-9 are Expressed in Allergic but not in Irritant Patch Test Reactions

Flier, Jacoba; Boorsma, D. M.; Bruynzeel, Derk P.; Beek, Peter J. van; Stoof, T.J.; Scheper, Rik J.; Willemze, Rein; Tensen, Cornelis P.

doi:10.1046/j.1523-1747.1999.00730.x

Cited by 120 publications

(93 citation statements)

References 32 publications

(39 reference statements)

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“…Recently, Flier and colleagues 31 demonstrated that at later time points (Ͼ48 hours) MIG, IP-10, and IP-9 are essentially only detected in allergic but not in irritant patch-test reactions thus supporting our concept that at early time points the clinically invisible irritative inflammatory reaction is dominating whereas at later time points the immunological response evolves. During the later phase, strong expression of the IFN-␥-inducible chemokines IP-10 and MIG that is accompanied by a moderate expression of MIP-1␣/␤ may activate and preferentially attract T H1 cells that express CXCR3 and CCR5, respectively.…”

Section: Discussionsupporting

confidence: 56%

Differential and Sequential Expression of Multiple Chemokines during Elicitation of Allergic Contact Hypersensitivity

Goebeler¹,

Trautmann²,

Voss³

et al. 2001

The American Journal of Pathology

165

150

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Regulation of chemokine-mediated leukocyte migration within inflammatory tissues is a complex event that cannot be mimicked and analyzed in vitro.Hapten-induced contact hypersensitivity (CHS) is a highly frequent, often occupationally related human skin disorder in industrialized countries with an enormous sociomedical impact. 1 Moreover, CHS is considered as a standard model for an antigen-specific, T-lymphocytemediated immune response. 2 This concept still holds true for the clinically nonapparent sensitization phase of CHS with antigen-processing and presentation by Langerhans cells and a consecutive T cell stimulation in the draining lymph node. However, there is increasing evidence that during the clinically visible and physically disturbing elicitation phase of CHS nonspecific hapten-induced proinflammatory effects precede or parallel the antigen-specific effect and are a conditio sine qua non for the vigorous inflammatory reactions. 2 In a mouse CHS model Grabbe and colleagues 3 demonstrated that nonspecific effects of epicutaneously applied haptens contribute to the elicitation of CHS. Proinflammatory irritative rather than antigen-specific properties of the hapten are furthermore responsible for the strict concentration-dependence of the effector phase of CHS. Therefore, it is tempting to speculate that such irritative properties of haptens promote inflammatory skin reactions via induction of proinflammatory cytokines, adhesion molecules, and chemoattractants. Accordingly, some contact allergens such as urushiol, the relevant hapten in poison ivy, and nickel sulfate have been demonstrated to directly induce inflammatory activation of keratinocytes resulting in expression of ICAM-1, interleukin (IL)-8, and/or tumor necrosis factor (TNF)-␣. 4 -6 In recent years, in particular chemokines have emerged as potent stimulators of effector cell accumulation and activation and are likely candidates to mediate leukocyte recruitment during elicitation of CHS. Since the description of IL-8 more than a decade ago, the supergene Supported by grants from the W. Sander-Stiftung (95.064.2) (to R. G.) and from the Deutsche Forschungsgemeinschaft (811/1-3) to M. G. M. G. and A. Trautmann contributed equally to this work.

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Section: Discussionsupporting

confidence: 56%

Differential and Sequential Expression of Multiple Chemokines during Elicitation of Allergic Contact Hypersensitivity

Goebeler¹,

Trautmann²,

Voss³

et al. 2001

The American Journal of Pathology

165

150

View full text Add to dashboard Cite

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“…Recently, in situ hybridization studies have demonstrated that IP-10, I-TAC, and Mig are expressed in ACD reactions to nickel, where IP-10 and I-TAC are the most abundant and predominantly expressed by keratinocytes, whereas Mig is found in both the epidermis and dermis (21). In addition to chemokine expression, T lymphocytes infiltrating ACD skin express CXCR3, the cognate receptor for IP-10, I-TAC, and Mig (21).…”

Section: Cxcr3 Is Expressed By T Lymphocytes Infiltrating Acd Skinmentioning

confidence: 99%

“…In addition to chemokine expression, T lymphocytes infiltrating ACD skin express CXCR3, the cognate receptor for IP-10, I-TAC, and Mig (21). To further characterize the cell types that express CXCR3, double immunostaining of skin biopsies from 24-h-and 48-h-positive patch test reactions to nickel was performed.…”

Section: Cxcr3 Is Expressed By T Lymphocytes Infiltrating Acd Skinmentioning

confidence: 99%

IL-4 Enhances Keratinocyte Expression of CXCR3 Agonistic Chemokines

Albanesi

Scarponi

Sebastiani

et al. 2000

The Journal of Immunology

109

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IFN-induced protein of 10 kDa (IP-10), monokine induced by IFN-γ (Mig), and IFN-inducible T-cell α-chemoattractant (I-TAC) belong to the non-glutamate-leucine-arginine motif CXC chemokine family and act solely through the CXCR3 receptor for potent attraction of T lymphocytes. In this study, we evaluated the capacity of the T cell-derived cytokines IL-4, IL-10, and IL-17 to modulate IP-10, Mig, and I-TAC in cultured human keratinocytes and CXCR3 expression in T cells from allergic contact dermatitis (ACD). IL-4, but not IL-10 or IL-17, significantly up-regulated IFN-γ- or TNF-α-induced IP-10, Mig, and I-TAC mRNA accumulation in keratinocytes and increased the levels of IP-10 and Mig in keratinocyte supernatants. Immunohistochemistry of skin affected by ACD revealed that >70% of infiltrating cells were reactive for CXCR3 and that CXCR3 staining colocalized in CD4+ and CD8+ T cells. Nickel-specific CD4+ and CD8+ T cell lines established from ACD skin produced IFN-γ and IL-4 and expressed moderate to high levels of CXCR3. Finally, CXCR3 agonistic chemokines released by stimulated keratinocytes triggered calcium mobilization in skin-derived nickel-specific CD4+ T cells and promoted their migration, with supernatant from keratinocyte cultures stimulated with IFN-γ and IL-4 attracting more efficaciously than supernatant from keratinocytes activated with IFN-γ alone. In conclusion, IL-4 exerts a proinflammatory function on keratinocytes by potentiating IFN-γ and TNF-α induction of IP-10, Mig, and I-TAC, which in turn may determine a prominent recruitment of CXCR3+ T lymphocytes at inflammatory reaction sites.

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“…However, type 1 T cells appear massively attracted into the skin by keratinocyte release of the CXCR3 ligands, CXCL10, CXCL9/monokine induced by IFN-␥, and CXCL11/ IFN-induced T cell ␣-chemoattractant (5, 10). CXCR3 ligands appear deeply involved in type 1 T cell-mediated diseases such as allergic contact dermatitis and psoriasis, but are not relevantly expressed during skin response to irritants (5,11). Finally, CXCL8 is the best characterized of a group of chemoattractants active in neutrophil recruitment as well as in epithelial and endothelial cell proliferation (3,12).…”

mentioning

confidence: 99%

ERK1/2 Regulates Epidermal Chemokine Expression and Skin Inflammation

Pastore

Mascia

Mariotti

et al. 2005

The Journal of Immunology

164

169

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Resident cell populations of the skin contribute to the inflammatory response by producing an array of chemokines, which attract leukocytes from the circulation. TNF-α is a major inducer of proinflammatory mediators in keratinocytes. We have recently observed that epidermal growth factor receptor (EGFR) signaling affects TNF-α-driven chemokine expression in epidermal keratinocytes, and its functional impairment increases the levels of crucial chemoattractants such as CCL2/MCP-1, CCL5/RANTES, and CXCL10/IFN-γ-inducible protein-10. In this study, we report evidence that EGFR-dependent ERK1/2 activity is implicated in this mechanism. Abrogation of ERK1/2 activity with specific inhibitors increased chemokine expression in keratinocytes by enhancing mRNA stabilization. In mouse models, inflammatory response to irritants and T cell-mediated contact hypersensitivity were both aggravated when elicited in a skin area previously treated with an EGFR or a MAPK kinase 1/2 inhibitor. In contrast, impairment of p38αβ MAPK phosphorylation markedly attenuated these responses. Our data indicate that EGFR-dependent ERK1/2 activity in keratinocytes takes part to a homeostatic mechanism regulating inflammatory responses, and emphasize the distinct role of MAPKs as potential targets for manipulating inflammation in the skin.

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The CXCR3 Activating Chemokines IP-10, Mig, and IP-9 are Expressed in Allergic but not in Irritant Patch Test Reactions

Cited by 120 publications

References 32 publications

Differential and Sequential Expression of Multiple Chemokines during Elicitation of Allergic Contact Hypersensitivity

Differential and Sequential Expression of Multiple Chemokines during Elicitation of Allergic Contact Hypersensitivity

IL-4 Enhances Keratinocyte Expression of CXCR3 Agonistic Chemokines

ERK1/2 Regulates Epidermal Chemokine Expression and Skin Inflammation

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