Oncostatin M Expression Is Functionally Connected to Neutrophils in the Early Inflammatory Phase of Skin Repair: Implications for Normal and Diabetes-Impaired Wounds

Goren, Itamar; Kämpfer, Heiko; Müller, Elke; Schiefelbein, Dana; Pfeilschifter, Josef; Frank, Stefan

doi:10.1038/sj.jid.5700136

Cited by 49 publications

(37 citation statements)

References 36 publications

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“…42 However, under conditions of reduced wound tissue macrophages, our data suggest that TGF-␤1 might not be of importance in the control of inflammatory re- sponses of wound keratinocytes, as wound lysates of DTox-and PBS-treated lysM-Cre/DTR mice did not differ in bioavailable TGF-␤. By contrast, neutrophils are wellknown producers of pro-inflammatory cytokines such as IL-1␤, 10,43,44 a cytokine that was indeed increased in macrophage-depleted and neutrophil-infiltrated wounds (this study). Neutralization of IL-1 bioactivity from macrophage-depleted wound homogenates reduced the po- tency of homogenates to stimulate keratinocyte chemokine production to levels found in control mice.…”

Section: Discussionmentioning

confidence: 77%

A Transgenic Mouse Model of Inducible Macrophage Depletion

Goren

Allmann

Yogev

et al. 2009

The American Journal of Pathology

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322

151

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Whether the wound macrophage is a key regulatory inflammatory cell type in skin repair has been a matter of debate. A transgenic mouse model mediating inducible macrophage depletion during skin repair has not been used to date to address this question. Here, we specifically rendered the monocyte/macrophage leukocyte lineage sensitive to diphtheria toxin by expressing the lysozyme M promoter-driven, Cremediated excision of a transcriptional STOP cassette from the simian DT receptor gene in mice (lysM-Cre/ DTR). Application of diphtheria toxin to lysM-Cre/ DTR mice led to a rapid reduction in both skin tissue and wound macrophage numbers at sites of injury. Macrophage-depleted mice revealed a severely impaired wound morphology and delayed healing. In the absence of macrophages, wounds were re-populated by large numbers of neutrophils. Accordingly, macrophage-reduced wound tissues exhibited the increased and prolonged persistence of macrophage inflammatory protein-2, macrophage chemoattractant protein-1, interleukin-1␤, and cyclooxygenase-2, paralleled by unaltered levels of bioactive transforming growth factor-␤1. Altered expression patterns of vascular endothelial growth factor on macrophage reduction were associated with a disturbed neo-vascularization at the wound site. Impaired wounds revealed a loss of myofibroblast differentiation and wound contraction. Our data in the use of lysM-Cre/ DTR mice emphasize the pivotal function of wound macrophages in the integration of inflammation and cellular movements at the wound site to enable efficient skin repair.

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Section: Discussionmentioning

confidence: 77%

A Transgenic Mouse Model of Inducible Macrophage Depletion

Goren

Allmann

Yogev

et al. 2009

The American Journal of Pathology

Self Cite

322

151

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“…Our results also showed a marked infiltration of neutrophils in the dermis after skin exposure to AdOSM, which is consistent with elevated CXCL3 expression. Neutrophil accumulation in skin lesions is a feature of human psoriasis and these cells were described as a potential source of OSM, IL-1β, and IL-17 [30,35]. In addition, an important monocyte infiltrate was also observed in the skin of AdOSM-treated mice, which could be a source of TNF-α.…”

Section: Discussionmentioning

confidence: 97%

“…Although we clearly showed a direct activity of OSM on keratinocytes in vitro, we could hypothesize that, in vivo, it might also act directly or indirectly on other cell types such as dermal fibroblasts or skin resident immune cells, to promote skin inflammation. For example, OSMRβ expression has been reported on fibroblastic cells and infiltrating macrophages [30] and OSM has been shown to induce the expression of CCL1, CCL7, and CCL8 by primary dermal fibroblasts [31]. In addition, other proinflammatory cytokines might be released secondarily at the site of AdOSM injection and could contribute to synergistic effects with OSM.…”

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confidence: 99%

Oncostatin M overexpression induces skin inflammation but is not required in the mouse model of imiquimod‐induced psoriasis‐like inflammation

et al. 2016

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Oncostatin M (OSM) has been reported to be overexpressed in psoriasis skin lesions and to exert proinflammatory effects in vitro on human keratinocytes. Here, we report the proinflammatory role of OSM in vivo in a mouse model of skin inflammation induced by intradermal injection of murine OSM-encoding adenovirus (AdOSM) and compare with that induced by IL-6 injection. Here, we show that OSM potently regulates the expression of genes involved in skin inflammation and epidermal differentiation in murine primary keratinocytes. In vivo, intradermal injection of AdOSM in mouse ears provoked robust skin inflammation with epidermal thickening and keratinocyte proliferation, while minimal effect was observed after AdIL-6 injection. OSM overexpression in the skin increased the expression of the S100A8/9 antimicrobial peptides, CXCL3, CCL2, CCL5, CCL20, and Th1/Th2 cytokines, in correlation with neutrophil and macrophage infiltration. In contrast, OSM downregulated the expression of epidermal differentiation genes, such as cytokeratin-10 or filaggrin. Collectively, these results support the proinflammatory role of OSM when it is overexpressed in the skin. However, OSM expression was not required in the murine model of psoriasis induced by topical application of imiquimod, as demonstrated by the inflammatory phenotype of OSM-deficient mice or wild-type mice treated with anti-OSM antibodies.Keywords: Imiquimod · Keratinocyte · Oncostatin M · Psoriasis · Skin inflammation Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Jean-François Jégou e-mail: jean-francois.jegou@univ-poitiers.fr IntroductionPsoriasis is the most common inflammatory skin disease affecting 2-3% of the adult population, mainly in developed countries, Eur. J. Immunol. 2016Immunol. . 46: 1737Immunol. -1751 in which patients develop skin lesions characterized by erythematous and scaly plaques [1]. The histological features of psoriatic skins are a thickening of the epidermis resulting from an altered keratinocyte differentiation associated with a hyperplasia at the basement membrane, a hyperkeratosis and a parakeratosis (loss of the granular layer and abnormal presence of cell nuclei in the cornified layer) [1,2]. At the inflammatory site, these alterations of the epidermis are the consequence of a crosstalk between infiltrating immune cells and tissue resident cells (e.g. dermal fibroblasts, epidermal keratinocytes, and resident immune cells) through the release of numerous cytokines. In this complex network of interactions, keratinocytes are now considered to play a key role as bona fide innate immune cells, capable of secreting cytokines, chemokines, and antimicrobial peptides in response to various stimuli [3]. Psoriasis has been reported to be a Th1-and Th17-driven pathology [4]. The IL-23/IL-17 axis plays a crucial role in the pathogenesis of the disease, as demonstrated by the detection of IL-23 producing DCs and the expression of IL-17 and IL-22 by T cells and type 3...

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“…Sakai et al detected several cytokines in GCF using a cytokine antibody array system, including both inflammatory cytokines and various growth factors in periodontal healthy and chronic periodontitis subjects and found significant differences between healthy and diseased subjects' cytokine levels including OSM (Sakai et al, 2006). Again, the increased OSM expression and its role in the pathogenesis of various systemic diseases such as atherosclerosis (Modur et al, 1997), rheumatoid arthritis (Hui et al, 1997), multiple myeloma (Halin et al, 2000), and wound biology (Goren et al, 2006) have been evaluated. However, it has also been recognized that OSM exhibits unique activities that are not shared with the leukemia inhibitory factor (LIF) and accumulating evidence indicates that OSM is a unique cytokine that plays an important role for various biological systems such as inflammatory response, hematopoiesis, tissue remodeling, and development (Bruce et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Correlation of Levels of Oncostatin M Cytokine in Crevicular Fluid and Serum in Periodontal Disease

Thorat

Garg

2010

Int J Oral Sci

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Aim The aim of this study was to measure the level of Oncostatin M (OSM) a gp130 cytokine in the gingival crevicular fluid (GCF) and serum of chronic periodontitis patients and to find any correlation between them before and after periodontal therapy (scaling and root planing, SRP).Methodology 60 subjects (age 25-50 years) were enrolled into three groups (n=20 per group), group Ⅰ (healthy), group Ⅱ (gingivitis) and group III (chronic periodontitis). Group Ⅲ subjects were followed for 6-8 weeks after the initial periodontal therapy (SRP) as the group Ⅳ (after periodontal therapy). Clinical parameters were assessed as gingival index (GI), probing depth (PD), clinical attachment level (CAL), and radiographic evidence of bone loss. GCF and serum levels of OSM were measured by using Enzyme Linked Immunosorbent Assay (ELISA). ) and was found as below the detectable limit (≈0.0 pg·mL -1 ) in the serum of same subjects. Significant correlation has been found between clinical parameters and GCF-serum levels of OSM. ResultsConclusion Increased OSM level both in the GCF and serum, and the decreased levels after initial periodontal therapy (SRP) may suggest a use as an inflammatory biomarker in the periodontal disease.

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Oncostatin M Expression Is Functionally Connected to Neutrophils in the Early Inflammatory Phase of Skin Repair: Implications for Normal and Diabetes-Impaired Wounds

Cited by 49 publications

References 36 publications

A Transgenic Mouse Model of Inducible Macrophage Depletion

A Transgenic Mouse Model of Inducible Macrophage Depletion

Oncostatin M overexpression induces skin inflammation but is not required in the mouse model of imiquimod‐induced psoriasis‐like inflammation

Correlation of Levels of Oncostatin M Cytokine in Crevicular Fluid and Serum in Periodontal Disease

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