Human keratinocytes express fractalkine/CX3CL1
Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Journal of Dermatological Science
(Impact Factor: 3.42).
06/2003; 31(3):179-87. DOI: 10.1016/S0923-1811(03)00031-8
fractalkine/CX3CL1 is a unique chemokine that has properties of both chemoattractants and adhesion molecules. The major source of this chemokine in the skin is still controversial.
studies were undertaken to determine the expression of fractalkine in human skin.
RT-PCR, Western blotting, and immunostaining were performed with normal human epidermal keratinocytes (NHEK) and HaCaT cells, human keratinocyte cell line, for the presence of fractalkine. Biopsy specimens of normal and diseased skin were also investigated.
we identified that NHEK and HaCaT cells expressed fractalkine mRNA and protein. The combination of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma upregulated their expression by NHEK. Immunohistochemistry demonstrated fractalkine expression in keratinocytes in lichen planus and psoriasis vulgaris. RT-PCR also showed that lesional skin of psoriatic patients expressed higher levels of fractalkine mRNA than non-lesional skin from the same patients.
these results suggests that keratinocytes strongly express fractalkine in lichen planus and psoriasis vulgaris and that the fractalkine-CXC3CR1 system in the diseased skin can be a target for the treatment.
Available from: Martha Estrella García-Pérez
- "Additionally, TNF-α can increase the production of other multifunctional molecules such as prostaglandin E 2 (PGE 2 ) (Kanda and Watanabe, 2006) and nitric oxide (NO) by normal human and murine keratinocytes (Sirsjo et al., 1996; Yamaoka et al., 2000). Stimulation of NHK with TNF-α and IFN-γ induces an enhanced expression of fractalkine, a chemokine overexpressed in psoriatic skin which acts as chemoattractant and adhesion molecule (Raychaudhuri et al., 2001; Sugaya et al., 2003). Treatment of NHK with TNF-α also results in an increase of elafin expression at both the mRNA and the protein levels (Pfundt et al., 2000). "
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ABSTRACT: Ethnopharmacological relevance:
Picea mariana ((Miller) Britton, Sterns, and Poggenburg; Pinaceae) bark has been traditionally used by North American natives for treating topical inflammations. It has been also suggested to improve various inflammatory skin disorders like Psoriasis vulgaris. Extracts from this bark storage protein contain polyphenolic compounds which have well-known antiinflammatory activities. Based on the capacity of polyphenolic compounds to modulate functions of normal human keratinocytes, this study was set up to decipher the mechanisms of action of a chemically characterized polyphenolic extract from Picea mariana bark (BS-EAcf) on lesional keratinocytes of skin with psoriasis vulgaris, a disease driven by the immune system in which TNF-α plays a significant role.
Materials and methods:
BS-EAcf corresponds to the ethyl acetate soluble fraction from the hot water extract of Picea mariana bark. BS-EAcf effects were evaluated in normal human (NHK) and psoriatic (PK) keratinocytes stimulated by TNF-α. Cell viability was assessed by lactate deshydrogenase release and propidium iodide (PI) staining. The mechanisms of action of BS-EAcf in keratinocytes were investigated by flow cytometry, ELISAs, RT-PCR and western blot analyses.
PK exhibited a higher response to TNF-α than NHK regarding the ICAM-1 expression and the production of NO, IL-6, IL-8, fractalkine and PGE2, whereas BS-EAcf significantly inhibited this TNF-α-induced increase at concentrations without causing keratinocyte toxicity. Additionally, this extract significantly inhibited the TNF-α-induced release of elafin and VEGF by PK and NHK. Since TNF-α activation of most of these factors is dependent on the NF-κB pathway, this latter was studied in TNF-α-activated PK. BS-EAcf inhibited the TNF-α-induced phosphorylation and degradation of total IκBα as well as phosphorylation of NF-κB p65.
The ethyl acetate fraction from Picea mariana bark extract showed inhibitory effects of cytokines, chemokines, adhesion molecules, nitric oxide and prostaglandins produced by keratinocytes under TNF-α activation through down-regulating the NF-κB pathway. This study demontrated that this extract could be a potential antiinflammatory agent capable of improving psoriatic skin.
Available from: Anthony James P Clover
- "Interestingly FKN is also expressed on human keratinocytes  but its role is as yet unknown. We hypothesized that Fractalkine and CX3CR1 have a role in burn wound healing by contributing to the myeloid cell recruitment and improving angiogenesis in the burn wound. "
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ABSTRACT: The development of a good blood supply is a key step in burn wound healing and appears to be regulated in part by myeloid cells. CX3CR1 positive cells have recently been identified as myeloid cells with a potential role in angiogenesis. The role of functional CX3CR1 system in burn wound healing is not previously investigated. A 2% contact burn was induced in CX3CR1(+/gfp) and CX3CR1(gfp/gfp) mice. These transgenic mice facilitate the tracking of CX3CR1 cells (CX3CR1(+/gfp)) and allow evaluation of the consequence of CX3CR1 functional knockout (CX3CR1(gfp/gfp)) on burn wound healing. The progression of wound healing was monitored before tissue was harvested and analyzed at day 6 and day 12 for migration of CX3CR1 cells into burn wound. Deficiency of a functional CX3CR1 system resulted in decreased recruitment of CX3CR1 positive cells into the burn wound associated with decreased myeloid cell recruitment (p<0.001) and reduced maintenance of new vessels (p<0.001). Burn wound healing was prolonged (p<0.05). Our study is the first to establish a role for CX3CR1 in burn wound healing which is associated with sub-dermal angiogenesis. This chemokine receptor pathway may be attractive for therapeutic manipulation as it could increase sub dermal angiogenesis and thereby improve time to healing.
Available from: Harris A Gelbard
- "Soluble fractalkine can function as a chemotactic factor for monocytes, NK-cells, and T-cells expressing CX3CR1 (Bazan et al. 1997; Chapman et al. 2000). Current evidence indicates that fractalkine is expressed constitutively in neurons within specific regions of the brain and in epithelial cells in epidermal tissues and the intestine (Lucas et al. 2001; Hughes et al. 2002; Sugaya et al. 2003). Fractalkine expression is upregulated by endothelial and epithelial cells in epidermal, renal, bronchial, intestinal, and hepatic tissues in response to disease, inflammation , or application of inflammatory mediators (Harrison et al. 1999; Fujimoto et al. 2001; Lucas et al. 2001; Cockwell et al. 2002; Efsen et al. 2002; Hughes et al. 2002; Sugaya et al. 2003). "
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ABSTRACT: Human fractalkine (CX3CL1), a delta-chemokine, is implicated in the mediation of multiple cell functions. In addition to serving as a chemotactic factor for mononuclear cell subtypes, membrane-bound fractalkine may promote viral infection by interacting with virions that encode putative fractalkine-binding proteins. Fractalkine expression in normal epithelial tissues studied to date is either constitutive or is upregulated with inflammation. In salivary glands, the expression of fractalkine is unknown. Moreover, salivary glands are a major site for the persistent and productive infection by human herpesvirus (HHV)-7, which encodes two putative fractalkine-binding gene products, U12 and U51. Surprisingly, the cellular distribution of HHV-7 in major salivary glands has not been explored. We therefore determined by immunohistochemistry the cellular localization of fractalkine in three different salivary glands: parotid, submandibular, and labial glands. Fractalkine expression was highly variable, ranging from high to undetectable levels. We further examined the association of fractalkine with inflammatory cell infiltration or HHV-7 infection of salivary epithelial cells. Inflammatory cells were always adjacent to epithelial cells expressing fractalkine, consistent with a function of fractalkine in inflammatory cell recruitment and/or retention in salivary glands. In contrast, HHV-7-infected epithelial cells did not always express fractalkine, suggesting that fractalkine may not be an absolute requirement for viral entry.
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