CCL7 contributes to the TNF-alpha-dependent inflammation of lesional psoriatic skin.

Abstract

Chemokines are small chemotactic proteins that have a crucial role in leukocyte recruitment into tissue. Targeting these mediators has been suggested as a potential therapeutic option in inflammatory skin diseases such as psoriasis. Using quantitative RT-PCR, we found CCL7, a chemokine ligand known to interact with multiple C-C chemokine receptors, to be markedly increased in lesional psoriasis as opposed to atopic dermatitis, lichen planus, non-lesional psoriatic and normal control skin. Surprisingly, this increase in CCL7 mRNA expression exceeded that of all other chemokines investigated, and keratinocytes and dermal blood endothelial cells were identified as its likely cellular sources. In an imiquimod-induced psoriasis-like mouse model, CCL7 had a profound impact on myeloid cell inflammation as well as on the upregulation of key pro-psoriatic cytokines such as CCL20, IL-12p40 and IL-17C, while its blockade led to an increase in the antipsoriatic cytokine IL-4. In humans receiving the TNF-α-blocker infliximab, CCL7 was downregulated in lesional psoriatic skin already within 16 hours after a single intravenous infusion. These data suggest that CCL7 acts as a driver of TNF-α-dependent Th1/Th17-mediated inflammation in lesional psoriatic skin.

• Authors: Patrick M Brunner, Elisabeth Glitzner, Baerbel Reininger, Irene Klein, Georg Stary, Michael Mildner, Pavel Uhrin, Maria Sibilia, Georg Stingl
• Journal: Experimental dermatology (Exp Dermatol) Vol. 24 Issue 7 Pg. 522-8 (Jul 2015) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 25828150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• CCL7 protein, human
• Ccl7 protein, mouse
• Chemokine CCL7
• Inflammation Mediators
• Interleukin-1beta
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Infliximab

Topics

• Adolescent
• Adult
• Animals
• Case-Control Studies
• Chemokine CCL7 (genetics, metabolism)
• Dermatitis, Atopic (immunology)
• Disease Models, Animal
• Down-Regulation
• Endothelial Cells (immunology)
• Humans
• Inflammation Mediators (metabolism)
• Infliximab (pharmacology)
• Interleukin-1beta (metabolism)
• Keratinocytes (immunology)
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Psoriasis (etiology, immunology, pathology)
• RNA, Messenger (genetics, metabolism)
• Skin Diseases (immunology)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism)
• Young Adult