Leukocytes: The Double‐Edged Sword in Fibrosis

Kryczka, Jakub; Boncela, Joanna

doi:10.1155/2015/652035

Cited by 39 publications

(40 citation statements)

References 102 publications

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“…Chronic AI lesions feature immune cell infiltration and strong expression of numerous proinflammatory cytokines like TNF- α and IL-17A [11]. The inflammation seems to increase the destruction of skin architecture and the development of deep fistulating sinuses [12]. …”

Section: Introductionmentioning

confidence: 99%

MMP8 Is Increased in Lesions and Blood of Acne Inversa Patients: A Potential Link to Skin Destruction and Metabolic Alterations

Tsaousi

Witte

et al. 2016

Mediators of Inflammation

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Acne inversa (AI; also designated as hidradenitis suppurativa) is a chronic inflammatory disease with still unknown pathogenesis that affects the intertriginous skin of perianal, inguinal, and axillary sites. It leads to painful nodules, abscesses, and fistulas with malodorous secretion and is frequently associated with metabolic alterations. Here, we demonstrate that one of the most highly upregulated molecules in AI lesions is matrix metalloproteinase 8 (MMP8), an enzyme specialized in the degradation of extracellular matrix components and the HDL component apolipoprotein A-I. Granulocytes, which were present in AI lesions, secreted high amounts of MMP8 especially after TNF-α stimulation. Furthermore, activated fibroblasts but not keratinocytes were found to express MMP8. The high lesional MMP8 levels were accompanied by elevated blood levels that positively correlated with TNF-α blood levels and disease severity assessed by Sartorius score, especially with the number of regions with inflammatory nodules/abscesses and fistulas. Additionally, we found a negative correlation between blood MMP8 and HDL-cholesterol levels, suggesting a contributory role of MMP8 in metabolic alterations in AI. In summary, we demonstrate elevated MMP8 levels in AI lesions, suggest their role in skin destruction and metabolic alterations, and recommend the use of MMP8 as blood biomarker for AI disease activity assessment.

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Section: Introductionmentioning

confidence: 99%

MMP8 Is Increased in Lesions and Blood of Acne Inversa Patients: A Potential Link to Skin Destruction and Metabolic Alterations

Tsaousi

Witte

et al. 2016

Mediators of Inflammation

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“…For example, cardiac and renal fibrosis is associated with the emergence of fibroblasts originating from ECs (ECs are estimated to participate in more than 25% of fibroblast formation), supporting that EndMT could be involved in fibrosis development [11, 14]. Interestingly, macrophages releasing TGF-β (regulatory macrophages) promote fibroblast/myofibroblast switch as well as EndMT [15-18]. While in the early phase of fibrotic changes, cytoplasmic protein fibroblast-specific protein 1 (FSP1, also known as S100A-4) is produced, in latter phases, structural proteins including α-smooth muscle actin (α-SMA) are overexpressed [11].…”

Section: Introductionmentioning

confidence: 99%

Nitro-oleic acid inhibits vascular endothelial inflammatory responses and the endothelial-mesenchymal transition

Ambrožová

Fidlerova

Verescakova

et al. 2016

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background Inflammatory-mediated pathological processes in the endothelium arise as a consequence of the dysregulation of vascular homeostasis. Of particular importance are mediators produced by stimulated monocytes/macrophages inducing activation of endothelial cells (ECs). This is manifested by excessive soluble pro-inflammatory mediator production and cell surface adhesion molecule expression. Nitro-fatty acids are endogenous products of metabolic and inflammatory reactions that display immuno-regulatory potential and may represent a novel therapeutic strategy to treat inflammatory diseases. The purpose of our study was to characterize the effects of nitro-oleic acid (OA-NO2) on inflammatory responses and the endothelial-mesenchymal transition (EndMT) in ECs that is a consequence of the altered healing phase of the immune response. Methods The effect of OA-NO2 on inflammatory responses and EndMT was determined in murine macrophages and murine and human ECs using Western blotting, ELISA, immunostaining, and functional assays. Results OA-NO2 limited the activation of macrophages and ECs by reducing pro-inflammatory cytokine production and adhesion molecule expression through its modulation of STAT, MAPK and NF-κB-regulated signaling. OA-NO2 also decreased transforming growth factor-β-stimulated EndMT and pro-fibrotic phenotype of ECs. These effects are related to the downregulation of Smad2/3. Conclusions The study shows the pleiotropic effect of OA-NO2 on regulating EC-macrophage interactions during the immune response and suggests a role for OA-NO2 in the regulation of vascular endothelial immune and fibrotic responses arising during chronic inflammation. General significance These findings propose the OA-NO2 may be useful as a novel therapeutic agent for treatment of cardiovascular disorders associated with dysregulation of the endothelial immune response.

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“…Of the PSGs in the innate response, the cytokines interleukin 4 ( IL-4 ) and interleukin 33 ( IL-33 ) are essential components of the T H 2 immune response to helminths 42-48 . Additional positively selected genes consist of other cytokines and chemokines, including TNF, CXCL13 , and CD34 , which play critical roles in the recruitment of immune cells to injured tissues 49 . Furthermore, IL-17F recruits dermal innate immune cells during the inflammation and cell proliferation phases of wound response 50 ; and fibroblast growth factor1 (FGF1) is known to stimulate angiogenesis and tissue repair and to induce the proliferation of keratinocytes 51 , which are required for the final stage of wound healing.…”

Section: Resultsmentioning

confidence: 99%

Genomic perspectives on adaptation and conservation in the endangered long-tailed goral (Naemorhedus caudatus)

Chung

et al. 2018

Preprint

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Native to the mountains of East Asia, the long-tailed goral (Naemorhedus caudatus) is a vulnerable wild ungulate in the tribe Caprini. To understand key conservation issues related to fragmentation and subsequent endangerment of this montane species, we sequenced and analyzed the genome of a long-tailed goral to explore historical demography, contemporary levels of genetic diversity, and potential immune response. When compared to ten additional mammalian reference genomes, we identified 357 positively selected genes (PSGs) in the long-tailed goral and 364 PSGs in the Caprini lineage. Gene Ontology analyses showed statistical enrichment in biological processes related to immune function and in genes and pathways related to blood coagulation. We also identified low levels of heterozygosity (0.00114) in the long-tailed goral along with decreases in population size relative to other species of Caprini. Finally, we provide evidence for positive selection on the muscle development gene myostatin (MSTN) in the Caprini lineage, which may have increased the muscle development and climbing ability in the caprine common ancestor. Low effective population size and decreased heterozygosity of the long-tailed goral raise conservation concern about the effects of habitat fragmentation, over harvest, and inbreeding on this vulnerable species.

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Leukocytes: The Double‐Edged Sword in Fibrosis

Cited by 39 publications

References 102 publications

MMP8 Is Increased in Lesions and Blood of Acne Inversa Patients: A Potential Link to Skin Destruction and Metabolic Alterations

MMP8 Is Increased in Lesions and Blood of Acne Inversa Patients: A Potential Link to Skin Destruction and Metabolic Alterations

Nitro-oleic acid inhibits vascular endothelial inflammatory responses and the endothelial-mesenchymal transition

Genomic perspectives on adaptation and conservation in the endangered long-tailed goral (Naemorhedus caudatus)

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