Thrombospondin-1 triggers macrophage IL-10 production and promotes resolution of experimental lung injury

Zhao, Yani; Xiong, Zeyu; Lechner, Elizabeth J.; Klenotic, Philip A.; Hamburg, Brian J.; Hulver, Mei; Khare, Anupriya; Oriss, Timothy B.; Mangalmurti, Nilam S.; Chan, Yvonne R.; Zhang, Yingze; Ross, Mark A.; Stolz, Donna B.; Rosengart, Matthew R.; Pilewski, Joseph M.; Ray, Prabir; Ray, Anuradha; Silverstein, Roy L.; Lee, Janet

doi:10.1038/mi.2013.63

Cited by 71 publications

(71 citation statements)

References 42 publications

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“…However, in vivo studies appear to predominantly support the anti-inflammatory role of CD36. [41][42][43] In particular, reduced CD36 expression in respiratory as well as intestinal mucosa was associated with the development of inflammation. 42,43 In conjunctival epithelial cells, TSP-1:CD36 interaction is reported to activate the immunoregulatory cytokine, TGF-b.…”

Section: Discussionmentioning

confidence: 99%

“…9 In addition, our results indicate unaltered TSP-1 expression in EDE conjunctiva with significantly reduced CD36 expression, in contrast to the increased CD36 expression in TSP-1-deficient conjunctiva. Several in vitro studies have reported expression of both proinflammatory 37,38 and antiinflammatory [39][40][41] cytokines in macrophages resulting from the ligation of CD36 by ligands, such as apoptotic cells, oxidized low-density lipoprotein, and TSP-1, but not on epithelial cells. However, in vivo studies appear to predominantly support the anti-inflammatory role of CD36.…”

Section: Discussionmentioning

confidence: 99%

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Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

Soriano-Romaní

Contreras-Ruiz

García-Posadas

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Increased expression of transforming growth factor-b2 (TGF-b2) is reported in the conjunctiva of dry eye patients with no increase of anti-inflammatory activity of TGF-b2. Our aim was to compare the expression of molecules involved in TGF-b2 activation, thrombospondin-1 (TSP-1) and CD36, during murine and human conjunctival inflammation. Methods: Human conjunctival tissue from cadaveric donors, human conjunctival epithelial primary cells and fibroblasts, and murine conjunctivas were immunostained for TSP-1, CD36, or TGF-b2. Inflamed conjunctival tissues were obtained from C57BL/6 wild-type (WT) mice induced to develop experimental dry eye (EDE) with 10 days of desiccating conditions and scopolamine injections and TSP-1-deficient (TSP1 -/ -) mice, which spontaneously develop Sjögren's syndrome-associated conjunctival inflammation with age. Immunostaining intensities were compared using ImageJ software. Cultures of human conjunctival fibroblasts were stimulated with IL-1b and both secreted protein and message levels of TSP-1, CD36, and TGF-b2 were analyzed. Results: TSP-1 and CD36 were detectable in human and murine conjunctival tissues as well as primary conjunctival epithelial cells and fibroblasts. Increased conjunctival immunostaining of TGF-b2 and reduced CD36 were detected in EDE mice compared with WT mice. Interestingly, increased TGF-b2 and CD36 conjunctival immunostaining was detected in TSP1-/ -mice. The expression of TSP-1 and CD36 was downregulated in IL-1b-stimulated conjunctival fibroblasts at both the protein and message level, while active TGFb2 was undetected. Conclusions: The absence or reduced expression of either of the molecules involved in TGF-b2 activation supports proinflammatory conditions in the conjunctiva. Changes in TSP-1 and CD36 may serve as potential biomarkers of conjunctival inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

Soriano-Romaní

Contreras-Ruiz

García-Posadas

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

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“…Noteworthy transcripts in these categories/pathways included matrix metalloproteinase 25 (MMP25; aka MT-MMP6) (47), thrombospondin 1 (THBS1) (48,49), Toll-like receptor 1 (TLR1) (50, 51), TLR5 (52), chitinase 3-like 1 (CHIL3L1) (53,54), and IL 12b (IL12B) (55,56).…”

Section: Transcriptomic Analysismentioning

confidence: 99%

Secreted Phosphoprotein 1 Is a Determinant of Lung Function Development in Mice

Ganguly

Martin

Concel

et al. 2014

Am J Respir Cell Mol Biol

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Secreted phosphoprotein 1 (Spp1) is located within quantitative trait loci associated with lung function that was previously identified by contrasting C3H/HeJ and JF1/Msf mouse strains that have extremely divergent lung function. JF1/Msf mice with diminished lung function had reduced lung SPP1 transcript and protein during the peak stage of alveologenesis (postnatal day [P]14-P28) as compared with C3H/ HeJ mice. In addition to a previously identified genetic variant that altered runt-related transcription factor 2 (RUNX2) binding in the Spp1 promoter, we identified another promoter variant in a putative RUNX2 binding site that increased the DNA protein binding. SPP1 induced dose-dependent mouse lung epithelial-15 cell proliferation. Spp1(2/2) mice have decreased specific total lung capacity/body weight, higher specific compliance, and increased mean airspace chord length (L m ) compared with Spp1(1/1) mice. Microarray analysis revealed enriched gene ontogeny categories, with numerous genes associated with lung development and/or respiratory disease. Insulin-like growth factor 1, Hedgehog-interacting protein, winglessrelated mouse mammary tumor virus integration site 5A, and NOTCH1 transcripts decreased in the lung of P14 Spp1 (2/2) mice as determined by quantitative RT-PCR analysis. SPP1 promotes pneumocyte growth, and mice lacking SPP1 have smaller, more compliant lungs with enlarged airspace (i.e., increased L m ). Microarray analysis suggests a dysregulation of key lung developmental transcripts in gene-targeted Spp1 (2/2) mice, particularly during the peak phase of alveologenesis. In addition to its known roles in lung disease, this study supports SPP1 as a determinant of lung development in mice.

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“…Deficiency of TSP-1 has been reported to show contrasting effects in different experimental studies [26,28,29,58]. Lack of TSP-1 has been reported to promote inflammatory response to retinal injury and inflammatory mediated lung injury in C57BL/6 mice [28,58].…”

Section: Discussionmentioning

confidence: 99%

High serum thrombospondin-1 concentration is associated with slower abdominal aortic aneurysm growth and deficiency of thrombospondin-1 promotes angiotensin II induced aortic aneurysm in mice

et al. 2017

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Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Thrombospondin-1 (TSP-1; gene Thbs1) is a member of the matricellular protein family important in the control of extracellular matrix (ECM) remodelling. In the present study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeated ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration (Spearman's rho − 0.129, P=0.033). Men with TSP-1 in the highest quartile had a reduced likelihood of AAA growth greater than median during follow-up (OR: 0.40; 95% confidence interval (CI): 0.19-0.84, P=0.016, adjusted for other risk factors). Immunohistochemical staining for TSP-1 was reduced in AAA body tissues compared with the relatively normal AAA neck. To further assess the role of TSP-1 in AAA initiation and progression, combined TSP-1 and apolipoprotein deficient (Thbs1 −/− ApoE −/− , n=20) and control mice (ApoE −/− , n=20) were infused subcutaneously with angiotensin II (AngII) for 28 days. Following AngII infusion, Thbs1 −/− ApoE −/− mice had larger AAAs by ultrasound (P=0.024) and ex vivo morphometry measurement (P=0.006). The Thbs1 −/− ApoE −/− mice also showed increased elastin filament degradation along with elevated systemic levels and aortic expression of matrix metalloproteinase (MMP)-9. Suprarenal aortic segments and vascular smooth muscle cells (VSMCs) isolated from Thbs1 −/− ApoE −/− mice showed reduced collagen 3A1 gene expression. Furthermore, Thbs1 −/− ApoE −/− mice had reduced aortic expression of low-density lipoprotein (LDL) receptor-related protein 1. Collectively, findings from the present study suggest that TSP-1 deficiency promotes maladaptive remodelling of the ECM leading to accelerated AAA progression.

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Thrombospondin-1 triggers macrophage IL-10 production and promotes resolution of experimental lung injury

Cited by 71 publications

References 42 publications

Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

Secreted Phosphoprotein 1 Is a Determinant of Lung Function Development in Mice

High serum thrombospondin-1 concentration is associated with slower abdominal aortic aneurysm growth and deficiency of thrombospondin-1 promotes angiotensin II induced aortic aneurysm in mice

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