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The expression and regulation of chemerin in the epidermis.

Banas M, Zegar A, Kwitniewski M, Zabieglo K, Marczynska J, Kapinska-Mrowiecka M, LaJevic M, Zabel BA, Cichy J - PLoS ONE (2015)

Bottom Line: In human skin cultures, chemerin is significantly downregulated by IL-17 and IL-22, key cytokines implicated in psoriasis, whereas it is upregulated by acute phase cytokines oncostatin M and IL-1β.Furthermore, in a cutaneous infection model, chemerin is required for maximal bactericidal effects in vivo.Together, our findings reveal previously uncharacterized regulators of chemerin expression in skin and identify a physiologic role for chemerin in skin barrier defense against microbial pathogens.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.

ABSTRACT
Chemerin is a protein ligand for the G protein-coupled receptor CMKLR1 and also binds to two atypical heptahelical receptors, CCRL2 and GPR1. Chemerin is a leukocyte attractant, adipokine, and antimicrobial protein. Although chemerin was initially identified as a highly expressed gene in healthy skin keratinocytes that was downregulated during psoriasis, the regulation of chemerin and its receptors in the skin by specific cytokines and microbial factors remains unexplored. Here we show that chemerin, CMKLR1, CCRL2 and GPR1 are expressed in human and mouse epidermis, suggesting that this tissue may be both a source and target for chemerin mediated effects. In human skin cultures, chemerin is significantly downregulated by IL-17 and IL-22, key cytokines implicated in psoriasis, whereas it is upregulated by acute phase cytokines oncostatin M and IL-1β. Moreover, we show that human keratinocytes in vitro and mouse skin in vivo respond to specific microbial signals to regulate expression levels of chemerin and its receptors. Furthermore, in a cutaneous infection model, chemerin is required for maximal bactericidal effects in vivo. Together, our findings reveal previously uncharacterized regulators of chemerin expression in skin and identify a physiologic role for chemerin in skin barrier defense against microbial pathogens.

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Psoriasis-associated cytokines downregulate chemerin and acute phase cytokines upregulate chemerin expression in epidermis.Normal keratinocytes grown in 3D culture were treated with the indicated factors for 24 (A-B) or 48h (C-D). Total RNA was subjected to RT-QPCR. Relative expression of stimulated cells over control is shown as the mean ±SD from five-nine independent experiments (A, C). Levels of secreted chemerin were determined in parallel in conditioned media by ELISA. Data show the mean ±SD from five-nine independent experiments (B, D). Statistical significance between control and the treated cells is shown by asterisk; *p<0.05 by ANOVA followed by a Bonferroni post hoc test.
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pone.0117830.g003: Psoriasis-associated cytokines downregulate chemerin and acute phase cytokines upregulate chemerin expression in epidermis.Normal keratinocytes grown in 3D culture were treated with the indicated factors for 24 (A-B) or 48h (C-D). Total RNA was subjected to RT-QPCR. Relative expression of stimulated cells over control is shown as the mean ±SD from five-nine independent experiments (A, C). Levels of secreted chemerin were determined in parallel in conditioned media by ELISA. Data show the mean ±SD from five-nine independent experiments (B, D). Statistical significance between control and the treated cells is shown by asterisk; *p<0.05 by ANOVA followed by a Bonferroni post hoc test.

Mentions: To facilitate our studies investigating the mechanisms regulating chemerin expression in skin we generated pseudo-stratified, highly differentiated human epidermal tissue in vitro. In contrast to keratinocyte monolayers that do not fully recapitulate the multilayered differentiation of epidermis and express little-to-no chemerin ([27] and data not shown), this 3D tissue closely resembles the epidermis, and keratinocytes in these 3D cultures express high levels of chemerin Figs. 3 & 4. Importantly, the polarized nature of skin keratinocytes in this model allows for the anatomical segregation of epidermal responses. We applied cytokines to the basolateral compartment to mimic epidermal cytokine exposure resulting from immune cells infiltrating the skin [38,39,40,41].


The expression and regulation of chemerin in the epidermis.

Banas M, Zegar A, Kwitniewski M, Zabieglo K, Marczynska J, Kapinska-Mrowiecka M, LaJevic M, Zabel BA, Cichy J - PLoS ONE (2015)

Psoriasis-associated cytokines downregulate chemerin and acute phase cytokines upregulate chemerin expression in epidermis.Normal keratinocytes grown in 3D culture were treated with the indicated factors for 24 (A-B) or 48h (C-D). Total RNA was subjected to RT-QPCR. Relative expression of stimulated cells over control is shown as the mean ±SD from five-nine independent experiments (A, C). Levels of secreted chemerin were determined in parallel in conditioned media by ELISA. Data show the mean ±SD from five-nine independent experiments (B, D). Statistical significance between control and the treated cells is shown by asterisk; *p<0.05 by ANOVA followed by a Bonferroni post hoc test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4320080&req=5

pone.0117830.g003: Psoriasis-associated cytokines downregulate chemerin and acute phase cytokines upregulate chemerin expression in epidermis.Normal keratinocytes grown in 3D culture were treated with the indicated factors for 24 (A-B) or 48h (C-D). Total RNA was subjected to RT-QPCR. Relative expression of stimulated cells over control is shown as the mean ±SD from five-nine independent experiments (A, C). Levels of secreted chemerin were determined in parallel in conditioned media by ELISA. Data show the mean ±SD from five-nine independent experiments (B, D). Statistical significance between control and the treated cells is shown by asterisk; *p<0.05 by ANOVA followed by a Bonferroni post hoc test.
Mentions: To facilitate our studies investigating the mechanisms regulating chemerin expression in skin we generated pseudo-stratified, highly differentiated human epidermal tissue in vitro. In contrast to keratinocyte monolayers that do not fully recapitulate the multilayered differentiation of epidermis and express little-to-no chemerin ([27] and data not shown), this 3D tissue closely resembles the epidermis, and keratinocytes in these 3D cultures express high levels of chemerin Figs. 3 & 4. Importantly, the polarized nature of skin keratinocytes in this model allows for the anatomical segregation of epidermal responses. We applied cytokines to the basolateral compartment to mimic epidermal cytokine exposure resulting from immune cells infiltrating the skin [38,39,40,41].

Bottom Line: In human skin cultures, chemerin is significantly downregulated by IL-17 and IL-22, key cytokines implicated in psoriasis, whereas it is upregulated by acute phase cytokines oncostatin M and IL-1β.Furthermore, in a cutaneous infection model, chemerin is required for maximal bactericidal effects in vivo.Together, our findings reveal previously uncharacterized regulators of chemerin expression in skin and identify a physiologic role for chemerin in skin barrier defense against microbial pathogens.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.

ABSTRACT
Chemerin is a protein ligand for the G protein-coupled receptor CMKLR1 and also binds to two atypical heptahelical receptors, CCRL2 and GPR1. Chemerin is a leukocyte attractant, adipokine, and antimicrobial protein. Although chemerin was initially identified as a highly expressed gene in healthy skin keratinocytes that was downregulated during psoriasis, the regulation of chemerin and its receptors in the skin by specific cytokines and microbial factors remains unexplored. Here we show that chemerin, CMKLR1, CCRL2 and GPR1 are expressed in human and mouse epidermis, suggesting that this tissue may be both a source and target for chemerin mediated effects. In human skin cultures, chemerin is significantly downregulated by IL-17 and IL-22, key cytokines implicated in psoriasis, whereas it is upregulated by acute phase cytokines oncostatin M and IL-1β. Moreover, we show that human keratinocytes in vitro and mouse skin in vivo respond to specific microbial signals to regulate expression levels of chemerin and its receptors. Furthermore, in a cutaneous infection model, chemerin is required for maximal bactericidal effects in vivo. Together, our findings reveal previously uncharacterized regulators of chemerin expression in skin and identify a physiologic role for chemerin in skin barrier defense against microbial pathogens.

Show MeSH
Related in: MedlinePlus