Oncostatin M enhances CCL21 expression by microvascular endothelial cells and increases the efficiency of dendritic cell trafficking to lymph nodes

Makoto Sugaya, Lei Fang, Adela R. Cardones, Takashi Kakinuma, Samer H. Jaber, Andrew Blauvelt, Samuel T Hwang

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

CCL21, a lymphatic endothelial cell (LEC)-derived chemokine, and its receptor CCR7 regulate dendritic cell (DC) trafficking to lymph nodes (LN), but it is unclear how CCL21 expression is regulated. Oncostatin M (OSM) is an IL-6-like cytokine synthesized by activated DC and other leukocytes. In vitro, OSM (but not TNF-α) stimulated CCL21 mRNA and protein expression by human dermal microvascular EC (DMEC) in an ERK1/2-dependent fashion. Conditioned medium from OSM-treated DMEC stimulated CCL21-dependent chemotaxis of mouse bone marrow-derived DC (BMDC). Cultured BMDC expressed OSM, which was increased with the addition of LPS. Topical application of the contact-sensitizing hapten, trinitrochlorobenzene, resulted in enhanced OSM expression in the skin, whereas cutaneous injection of TNF-α did not. Injection of OSM into the footpad increased CCL21 mRNA expression in the draining LN by ∼10-fold and in mouse skin by ∼4-fold without increasing CCM7 mRNA. In vitro, OSM increased the permeability of DMEC and lung microvascular EC monolayers to FITC-dextran beads, and, in vivo, it enhanced accumulation of Evans blue dye in draining LN by ∼3-fold (p = 0.0291). Of note, OSM increased trafficking of BMDC injected in footpads to draining LN by 2-fold (p = 0.016). In summary, OSM up-regulates CCL21 expression in skin and draining regional LN. We propose that OSM is a regulator of CCL21 expression and endothelial permeability in skin, contributing to efficient migration of DC to regional LN.

Original languageEnglish (US)
Pages (from-to)7665-7672
Number of pages8
JournalJournal of Immunology
Volume177
Issue number11
StatePublished - Dec 1 2006
Externally publishedYes

Fingerprint

Oncostatin M
Dendritic Cells
Endothelial Cells
Lymph Nodes
Skin
Bone Marrow
Messenger RNA
Picryl Chloride
Evans Blue
Injections
Haptens
Chemokine Receptors
Capillary Permeability
Chemotaxis
Conditioned Culture Medium
Permeability
Interleukin-6
Leukocytes
Coloring Agents
Up-Regulation

ASJC Scopus subject areas

  • Immunology

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Oncostatin M enhances CCL21 expression by microvascular endothelial cells and increases the efficiency of dendritic cell trafficking to lymph nodes. / Sugaya, Makoto; Fang, Lei; Cardones, Adela R.; Kakinuma, Takashi; Jaber, Samer H.; Blauvelt, Andrew; Hwang, Samuel T.

In: Journal of Immunology, Vol. 177, No. 11, 01.12.2006, p. 7665-7672.

Research output: Contribution to journalArticle

Sugaya, Makoto ; Fang, Lei ; Cardones, Adela R. ; Kakinuma, Takashi ; Jaber, Samer H. ; Blauvelt, Andrew ; Hwang, Samuel T. / Oncostatin M enhances CCL21 expression by microvascular endothelial cells and increases the efficiency of dendritic cell trafficking to lymph nodes. In: Journal of Immunology. 2006 ; Vol. 177, No. 11. pp. 7665-7672.
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AU - Fang, Lei

AU - Cardones, Adela R.

AU - Kakinuma, Takashi

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AU - Blauvelt, Andrew

AU - Hwang, Samuel T

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N2 - CCL21, a lymphatic endothelial cell (LEC)-derived chemokine, and its receptor CCR7 regulate dendritic cell (DC) trafficking to lymph nodes (LN), but it is unclear how CCL21 expression is regulated. Oncostatin M (OSM) is an IL-6-like cytokine synthesized by activated DC and other leukocytes. In vitro, OSM (but not TNF-α) stimulated CCL21 mRNA and protein expression by human dermal microvascular EC (DMEC) in an ERK1/2-dependent fashion. Conditioned medium from OSM-treated DMEC stimulated CCL21-dependent chemotaxis of mouse bone marrow-derived DC (BMDC). Cultured BMDC expressed OSM, which was increased with the addition of LPS. Topical application of the contact-sensitizing hapten, trinitrochlorobenzene, resulted in enhanced OSM expression in the skin, whereas cutaneous injection of TNF-α did not. Injection of OSM into the footpad increased CCL21 mRNA expression in the draining LN by ∼10-fold and in mouse skin by ∼4-fold without increasing CCM7 mRNA. In vitro, OSM increased the permeability of DMEC and lung microvascular EC monolayers to FITC-dextran beads, and, in vivo, it enhanced accumulation of Evans blue dye in draining LN by ∼3-fold (p = 0.0291). Of note, OSM increased trafficking of BMDC injected in footpads to draining LN by 2-fold (p = 0.016). In summary, OSM up-regulates CCL21 expression in skin and draining regional LN. We propose that OSM is a regulator of CCL21 expression and endothelial permeability in skin, contributing to efficient migration of DC to regional LN.

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