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Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment.

Albanesi C, Scarponi C, Pallotta S, Daniele R, Bosisio D, Madonna S, Fortugno P, Gonzalvo-Feo S, Franssen JD, Parmentier M, De Pità O, Girolomoni G, Sozzani S - J. Exp. Med. (2008)

Bottom Line: Chemerin expression was localized mainly in fibroblasts, mast cells, and endothelial cells.Fibroblasts cultured from skin of psoriatic lesions expressed higher levels of chemerin messenger RNA and protein than fibroblasts from uninvolved psoriatic skin or healthy donors and promoted pDC migration in vitro in a chemerin-dependent manner.Therefore, chemerin expression specifically marks the early phases of evolving skin psoriatic lesions and is temporally strictly associated with pDC.

View Article: PubMed Central - PubMed

Affiliation: Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00167 Rome, Italy.

ABSTRACT
Psoriasis is a type I interferon-driven T cell-mediated disease characterized by the recruitment of plasmacytoid dendritic cells (pDC) into the skin. The molecules involved in pDC accumulation in psoriasis lesions are unknown. Chemerin is the only inflammatory chemotactic factor that is directly active on human blood pDC in vitro. The aim of this study was to evaluate the role of the chemerin/ChemR23 axis in the recruitment of pDC in psoriasis skin. Prepsoriatic skin adjacent to active lesions and early lesions were characterized by a strong expression of chemerin in the dermis and by the presence of CD15(+) neutrophils and CD123(+)/BDCA-2(+)/ChemR23(+) pDC. Conversely, skin from chronic plaques showed low chemerin expression, segregation of neutrophils to epidermal microabscesses, and few pDC in the dermis. Chemerin expression was localized mainly in fibroblasts, mast cells, and endothelial cells. Fibroblasts cultured from skin of psoriatic lesions expressed higher levels of chemerin messenger RNA and protein than fibroblasts from uninvolved psoriatic skin or healthy donors and promoted pDC migration in vitro in a chemerin-dependent manner. Therefore, chemerin expression specifically marks the early phases of evolving skin psoriatic lesions and is temporally strictly associated with pDC. These results support a role for the chemerin/ChemR23 axis in the early phases of psoriasis development.

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Selective expression of chemerin by fibroblasts isolated of psoriatic LS skin. (A) Chemerin expression was determined in fibroblast primary cultures prepared from skin cells isolated from healthy donors (five donors) as well as NLS and LS skin of the same psoriatic patients (six donors). Levels of mRNA expression were determined after normalization with 18S ribosomal RNA values. Horizontal lines indicate mean values for each experimental group. (B) Chemerin protein expression was evaluated by ELISA on supernatants from fibroblast cultures derived from NLS and LS psoriatic patients (10 donors) and healthy subject (10 donors) skin cells. Cells were stimulated or not with 10 μM retinoic acid (ATRA) or 1 μM calcitriol (Calc) for 24 h. Data are represented as fold of induction, with basal chemerin release being 321 ± 31, 436 ± 84, and 702 ± 110 pg/ml for healthy, NLS, and LS psoriatic cells, respectively. Error bars are SD of mean values of 10 different donors per group. *, P < 0.05.
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fig3: Selective expression of chemerin by fibroblasts isolated of psoriatic LS skin. (A) Chemerin expression was determined in fibroblast primary cultures prepared from skin cells isolated from healthy donors (five donors) as well as NLS and LS skin of the same psoriatic patients (six donors). Levels of mRNA expression were determined after normalization with 18S ribosomal RNA values. Horizontal lines indicate mean values for each experimental group. (B) Chemerin protein expression was evaluated by ELISA on supernatants from fibroblast cultures derived from NLS and LS psoriatic patients (10 donors) and healthy subject (10 donors) skin cells. Cells were stimulated or not with 10 μM retinoic acid (ATRA) or 1 μM calcitriol (Calc) for 24 h. Data are represented as fold of induction, with basal chemerin release being 321 ± 31, 436 ± 84, and 702 ± 110 pg/ml for healthy, NLS, and LS psoriatic cells, respectively. Error bars are SD of mean values of 10 different donors per group. *, P < 0.05.

Mentions: Chemerin production by fibroblasts was further evaluated in vitro using primary cell cultures. Consistent with the immunohistochemical findings, chemerin messenger RNA (mRNA) levels, evaluated by quantitative PCR, were significantly higher (>50%; P < 0.01) in fibroblasts obtained from LS psoriatic skin compared with those from NLS skin of the same patients (Fig. 3 A). Fibroblasts from healthy donors expressed levels of chemerin mRNA that were only slightly reduced compared with fibroblasts from uninvolved skin of psoriatic patients, suggesting that the different genetic background of psoriatic cells does not have an influence on the basal levels of chemerin expression. Regulation of chemerin production was investigated at the protein level in cultures of fibroblasts stimulated with some of the proinflammatory cytokines that characterize psoriatic plaque lesions (e.g., IFN-γ, IFN-α, TNF-α, and CXCL8) (27, 28) or with factors known to regulate fibroblast growth, such as retinoic acid, calcitriol, and TGF-β. Basal chemerin release from healthy donor and NLS psoriatic skin fibroblasts was similar (321 ± 31 vs. 436 ± 84 pg/ml; mean ± SD; P = 0.07), whereas LS psoriatic fibroblast cultures released higher amounts of chemerin (702 ± 110 pg/ml; P < 0.01), which is in agreement with mRNA data. Among the different experimental conditions tested, only calcitriol induced a significant up-regulation of chemerin production (P < 0.01). Retinoic acid induced only a minor increment of chemerin release (Fig. 3 B), whereas all the other agonists tested did not show any effect on chemerin basal production independent of the source of fibroblasts (not depicted). The three fibroblast types investigated, namely from healthy donor skin, and NLS and LS skin from the same patients with psoriasis showed the same degree of chemerin regulation independent of basal levels of chemerin production (Fig. 3 B).


Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment.

Albanesi C, Scarponi C, Pallotta S, Daniele R, Bosisio D, Madonna S, Fortugno P, Gonzalvo-Feo S, Franssen JD, Parmentier M, De Pità O, Girolomoni G, Sozzani S - J. Exp. Med. (2008)

Selective expression of chemerin by fibroblasts isolated of psoriatic LS skin. (A) Chemerin expression was determined in fibroblast primary cultures prepared from skin cells isolated from healthy donors (five donors) as well as NLS and LS skin of the same psoriatic patients (six donors). Levels of mRNA expression were determined after normalization with 18S ribosomal RNA values. Horizontal lines indicate mean values for each experimental group. (B) Chemerin protein expression was evaluated by ELISA on supernatants from fibroblast cultures derived from NLS and LS psoriatic patients (10 donors) and healthy subject (10 donors) skin cells. Cells were stimulated or not with 10 μM retinoic acid (ATRA) or 1 μM calcitriol (Calc) for 24 h. Data are represented as fold of induction, with basal chemerin release being 321 ± 31, 436 ± 84, and 702 ± 110 pg/ml for healthy, NLS, and LS psoriatic cells, respectively. Error bars are SD of mean values of 10 different donors per group. *, P < 0.05.
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fig3: Selective expression of chemerin by fibroblasts isolated of psoriatic LS skin. (A) Chemerin expression was determined in fibroblast primary cultures prepared from skin cells isolated from healthy donors (five donors) as well as NLS and LS skin of the same psoriatic patients (six donors). Levels of mRNA expression were determined after normalization with 18S ribosomal RNA values. Horizontal lines indicate mean values for each experimental group. (B) Chemerin protein expression was evaluated by ELISA on supernatants from fibroblast cultures derived from NLS and LS psoriatic patients (10 donors) and healthy subject (10 donors) skin cells. Cells were stimulated or not with 10 μM retinoic acid (ATRA) or 1 μM calcitriol (Calc) for 24 h. Data are represented as fold of induction, with basal chemerin release being 321 ± 31, 436 ± 84, and 702 ± 110 pg/ml for healthy, NLS, and LS psoriatic cells, respectively. Error bars are SD of mean values of 10 different donors per group. *, P < 0.05.
Mentions: Chemerin production by fibroblasts was further evaluated in vitro using primary cell cultures. Consistent with the immunohistochemical findings, chemerin messenger RNA (mRNA) levels, evaluated by quantitative PCR, were significantly higher (>50%; P < 0.01) in fibroblasts obtained from LS psoriatic skin compared with those from NLS skin of the same patients (Fig. 3 A). Fibroblasts from healthy donors expressed levels of chemerin mRNA that were only slightly reduced compared with fibroblasts from uninvolved skin of psoriatic patients, suggesting that the different genetic background of psoriatic cells does not have an influence on the basal levels of chemerin expression. Regulation of chemerin production was investigated at the protein level in cultures of fibroblasts stimulated with some of the proinflammatory cytokines that characterize psoriatic plaque lesions (e.g., IFN-γ, IFN-α, TNF-α, and CXCL8) (27, 28) or with factors known to regulate fibroblast growth, such as retinoic acid, calcitriol, and TGF-β. Basal chemerin release from healthy donor and NLS psoriatic skin fibroblasts was similar (321 ± 31 vs. 436 ± 84 pg/ml; mean ± SD; P = 0.07), whereas LS psoriatic fibroblast cultures released higher amounts of chemerin (702 ± 110 pg/ml; P < 0.01), which is in agreement with mRNA data. Among the different experimental conditions tested, only calcitriol induced a significant up-regulation of chemerin production (P < 0.01). Retinoic acid induced only a minor increment of chemerin release (Fig. 3 B), whereas all the other agonists tested did not show any effect on chemerin basal production independent of the source of fibroblasts (not depicted). The three fibroblast types investigated, namely from healthy donor skin, and NLS and LS skin from the same patients with psoriasis showed the same degree of chemerin regulation independent of basal levels of chemerin production (Fig. 3 B).

Bottom Line: Chemerin expression was localized mainly in fibroblasts, mast cells, and endothelial cells.Fibroblasts cultured from skin of psoriatic lesions expressed higher levels of chemerin messenger RNA and protein than fibroblasts from uninvolved psoriatic skin or healthy donors and promoted pDC migration in vitro in a chemerin-dependent manner.Therefore, chemerin expression specifically marks the early phases of evolving skin psoriatic lesions and is temporally strictly associated with pDC.

View Article: PubMed Central - PubMed

Affiliation: Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00167 Rome, Italy.

ABSTRACT
Psoriasis is a type I interferon-driven T cell-mediated disease characterized by the recruitment of plasmacytoid dendritic cells (pDC) into the skin. The molecules involved in pDC accumulation in psoriasis lesions are unknown. Chemerin is the only inflammatory chemotactic factor that is directly active on human blood pDC in vitro. The aim of this study was to evaluate the role of the chemerin/ChemR23 axis in the recruitment of pDC in psoriasis skin. Prepsoriatic skin adjacent to active lesions and early lesions were characterized by a strong expression of chemerin in the dermis and by the presence of CD15(+) neutrophils and CD123(+)/BDCA-2(+)/ChemR23(+) pDC. Conversely, skin from chronic plaques showed low chemerin expression, segregation of neutrophils to epidermal microabscesses, and few pDC in the dermis. Chemerin expression was localized mainly in fibroblasts, mast cells, and endothelial cells. Fibroblasts cultured from skin of psoriatic lesions expressed higher levels of chemerin messenger RNA and protein than fibroblasts from uninvolved psoriatic skin or healthy donors and promoted pDC migration in vitro in a chemerin-dependent manner. Therefore, chemerin expression specifically marks the early phases of evolving skin psoriatic lesions and is temporally strictly associated with pDC. These results support a role for the chemerin/ChemR23 axis in the early phases of psoriasis development.

Show MeSH
Related in: MedlinePlus