scholarly journals Correction to: Proteoglycan-4 is an essential regulator of synovial macrophage polarization and inflammatory macrophage joint infiltration

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Marwa Qadri ◽  
Gregory D. Jay ◽  
Ling X. Zhang ◽  
Tannin A. Schmidt ◽  
Jennifer Totonchy ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Synovial Macrophage ◽  
Proteoglycan 4 ◽  
Inflammatory Macrophage

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals Proteoglycan-4 is an essential regulator of synovial macrophage polarization and inflammatory macrophage joint infiltration

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Marwa Qadri ◽  
Gregory D. Jay ◽  
Ling X. Zhang ◽  
Tannin A. Schmidt ◽  
Jennifer Totonchy ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Membrane Thickness ◽  
Type I ◽  
Surface Markers ◽  
M1 Macrophages ◽  
Synovial Hyperplasia ◽  
Synovial Macrophage ◽  
Proteoglycan 4 ◽  
Inflammatory Macrophages ◽  
The Impact

Abstract Background Synovial macrophages perform a multitude of functions that include clearance of cell debris and foreign bodies, tissue immune surveillance, and resolution of inflammation. The functional diversity of macrophages is enabled by distinct subpopulations that express unique surface markers. Proteoglycan-4 (PRG4) is an important regulator of synovial hyperplasia and fibrotic remodeling, and the involvement of macrophages in PRG4’s synovial role is yet to be defined. Our objectives were to study the PRG4’s importance to macrophage homeostatic regulation in the synovium and infiltration of pro-inflammatory macrophages in acute synovitis and investigate whether macrophages mediated synovial fibrosis in Prg4 gene-trap (Prg4GT/GT) murine knee joints. Methods Macrophage phenotyping in Prg4GT/GT and Prg4+/+ joints was performed by flow cytometry using pan-macrophage markers, e.g., CD11b, F4/80, and surface markers of M1 macrophages (CD86) and M2 macrophages (CD206). Characterizations of the various macrophage subpopulations were performed in 2- and 6-month-old animals. The expression of inflammatory markers, IL-6, and iNOS in macrophages that are CD86+ and/or CD206+ was studied. The impact of Prg4 recombination on synovial macrophage populations of 2- and 6-month-old animals and infiltration of pro-inflammatory macrophages in response to a TLR2 agonist challenge was determined. Macrophages were depleted using liposomal clodronate and synovial membrane thickness, and the expression of fibrotic markers α-SMA, PLOD2, and collagen type I (COL-I) was assessed using immunohistochemistry. Results Total macrophages in Prg4GT/GT joints were higher than Prg4+/+ joints (p<0.0001) at 2 and 6 months, and the percentages of CD86+/CD206− and CD86+/CD206+ macrophages increased in Prg4GT/GT joints at 6 months (p<0.0001), whereas the percentage of CD86−/CD206+ macrophages decreased (p<0.001). CD86+/CD206− and CD86+/CD206+ macrophages expressed iNOS and IL-6 compared to CD86−/CD206+ macrophages (p<0.0001). Prg4 re-expression limited the accumulation of CD86+ macrophages (p<0.05) and increased CD86−/CD206+ macrophages (p<0.001) at 6 months. Prg4 recombination attenuated synovial recruitment of pro-inflammatory macrophages in 2-month-old animals (p<0.001). Clodronate-mediated macrophage depletion reduced synovial hyperplasia, α-SMA, PLOD2, and COL-I expressions in the synovium (p<0.0001). Conclusions PRG4 regulates the accumulation and homeostatic balance of macrophages in the synovium. In its absence, the synovium becomes populated with M1 macrophages. Furthermore, macrophages exert an effector role in synovial fibrosis in Prg4GT/GT animals.

An in vitro test system for compounds that modulate human inflammatory macrophage polarization

2018 ◽  
Vol 833 ◽  
pp. 328-338 ◽  
Author(s):  
Hiromi Shiratori ◽  
Carmen Feinweber ◽  
Sonja Luckhardt ◽  
Nadja Wallner ◽  
Gerd Geisslinger ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Test System ◽  
In Vitro Test ◽  
Vitro Test ◽  
Inflammatory Macrophage

scholarly journals Macrophage-associated pro-inflammatory state in human islets from obese individuals

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wei He ◽  
Ting Yuan ◽  
Kathrin Maedler
Keyword(s):  
Inflammatory Cytokines ◽  
Macrophage Polarization ◽  
Human Islets ◽  
Macrophage Phenotype ◽  
Inflammatory State ◽  
Obese Control ◽  
Inflammatory Macrophages ◽  
Inflammatory Macrophage ◽  
Pro Inflammatory Cytokines

AbstractObesity is associated with inflammatory macrophages in insulin responsive tissues and the resulting inflammatory response is a major contributor to insulin resistance. In insulin-producing pancreatic islets, the intra-islet accumulation of macrophages is observed in patients of type 2 diabetes (T2D), but such has not been investigated in obese individuals. Here, we show that pro-inflammatory cytokines (IL-1β, IL-6, and TNF), anti-inflammatory cytokines (IL-10 and TGF-β) and macrophage polarization markers (CD11c, CD163, and NOS2) were expressed in isolated human islets from non-diabetic donors. Clodronate-mediated depletion of resident macrophages revealed expression of IL1B and IL10 mostly from macrophages, while IL6, TNF, and TGFB1 came largely from a non-macrophage origin in human islets. NOS2 expression came exclusively from non-macrophage cells in non-obese individuals, while it originated also from macrophages in obese donors. Macrophage marker expression of CD68, CD163, and ITGAX was unchanged in islets of non-obese control and obese cohorts. In contrast, IL1B and NOS2 were significantly increased in islets from obese, compared to non-obese individuals, implying a more inflammatory macrophage phenotype in islets in obesity. Our study shows elevated macrophage-associated inflammation in human islets in obesity, which could be an initiating factor to the pro-inflammatory intra-islet milieu and contribute to the higher susceptibility to T2D in obese individuals.

scholarly journals Salmonella persisters undermine host immune defenses during antibiotic treatment

Science ◽  
2018 ◽  
Vol 362 (6419) ◽  
pp. 1156-1160 ◽  
Author(s):  
Daphne A. C. Stapels ◽  
Peter W. S. Hill ◽  
Alexander J. Westermann ◽  
Robert A. Fisher ◽  
Teresa L. Thurston ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Macrophage Polarization ◽  
Physiological State ◽  
Innate Immune Responses ◽  
Macrophage Infection ◽  
Immune Defenses ◽  
Type 3 Secretion System ◽  
Type 3 ◽  
Inflammatory Macrophage

Many bacterial infections are hard to treat and tend to relapse, possibly due to the presence of antibiotic-tolerant persisters. In vitro, persister cells appear to be dormant. After uptake of Salmonella species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understood. In this work, we show that Salmonella persisters arising during macrophage infection maintain a metabolically active state. Persisters reprogram macrophages by means of effectors secreted by the Salmonella pathogenicity island 2 type 3 secretion system. These effectors dampened proinflammatory innate immune responses and induced anti-inflammatory macrophage polarization. Such reprogramming allowed nongrowing Salmonella cells to survive for extended periods in their host. Persisters undermining host immune defenses might confer an advantage to the pathogen during relapse once antibiotic pressure is relieved.

scholarly journals RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Amy E. L. Stone ◽  
Richard Green ◽  
Courtney Wilkins ◽  
Emily A. Hemann ◽  
Michael Gale
Keyword(s):  
West Nile Virus ◽  
Virus Infection ◽  
Macrophage Polarization ◽  
West Nile Virus Infection ◽  
West Nile ◽  
Inflammatory Macrophage

scholarly journals The Effect of miR-146a on the Gene Expression of Immunoregulatory Cytokines in Human Mesenchymal Stromal Cells

2020 ◽  
Vol 21 (18) ◽  
pp. 6809
Author(s):  
Jung Hwa Ko ◽  
Joo Youn Oh
Keyword(s):  
Stromal Cells ◽  
Macrophage Activation ◽  
Macrophage Polarization ◽  
Activated Macrophages ◽  
Mirna Microarray ◽  
Immunoregulatory Cytokines ◽  
Hepatocyte Growth ◽  
Inflammatory Macrophage ◽  
Necrosis Factor ◽  
Inducible Gene

Mounting evidence indicates that microRNAs (miRNAs), including miR-146a, have an impact on the immunomodulatory activities of mesenchymal stem/stromal cells (MSCs). Suppression of inflammatory macrophage activation is one of the main immunomodulatory mechanisms of MSCs. Here, we investigated whether miR-146a in MSCs might play a role in the effects of MSCs on macrophage activation. A miRNA microarray revealed that miR-146a was the most highly upregulated miRNA in MSCs upon co-culture with activated macrophages. Inhibition of miR-146a in MSCs through miR-146a inhibitor transfection had a different effect on the expression of immunoregulatory factors secreted by MSCs. Pentraxin 3, tumor necrosis factor-inducible gene 6, and cyclooxygenase-2, which are well-known mediators of the immunomodulatory functions of MSCs, were significantly upregulated in MSCs after miR-146a knockdown. By contrast, hepatocyte growth factor and stanniocalcin 1, other immunoregulatory molecules expressed by MSCs, were downregulated by miR-146a knockdown. Consequently, the inhibition of miR-146a in MSCs did not change the overall effect of MSCs on the suppression of inflammatory macrophage activation or the induction of anti-inflammatory macrophage polarization.

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