scholarly journals Heparin inhibits proinflammatory and promotes anti-inflammatory macrophage polarization under hyperglycemic stress

2020 ◽  
Vol 295 (15) ◽  
pp. 4849-4857 ◽  
Author(s):  
Amina Abbadi ◽  
Jacqueline Loftis ◽  
Aimin Wang ◽  
Minjia Yu ◽  
Yan Wang ◽  
...  

Monocytes are rapidly recruited to sites of diabetic complications and differentiate into macrophages. Previously, we showed that rat kidney mesangial cells dividing during hyperglycemic stress abnormally synthesize hyaluronan (HA) in intracellular compartments. This initiates a stress response, resulting in an extracellular HA matrix after division that recruits inflammatory cells. Cell–cell communication among macrophages that are recruited into the glomeruli and the damaged rat mesangial cells leads to diabetic nephropathy, fibrosis, and proteinurea, which are inhibited in heparin-treated diabetic rats. In this study, we found that murine bone marrow–derived macrophages (BMDMs) and a human leukemic cell line, U937 cells, dividing in hyperglycemia also accumulate intracellular HA and that heparin inhibits the HA accumulation. Both cell types expressed increased levels of proinflammatory markers: inducible nitric-oxide synthase and tumor necrosis factor-α, when cultured under hyperglycemic stress, which was inhibited by heparin. Furthermore, the abnormal intracellular HA was also observed in peripheral blood monocytes derived from three different hyperglycemic diabetic mouse models: streptozotocin-treated, high-fat fed, and Ins2Akita. Moreover, peripheral blood monocytes in humans with type 2 diabetes and poorly controlled blood glucose levels (hemoglobin A1c (HbA1c) levels of >7) also had intracellular HA, whereas those with HbA1c of <7, did not. Of note, heparin increased the anti-inflammatory markers arginase 1 and interleukin-10 in murine BMDMs. We conclude that heparin treatment of high glucose–exposed dividing BMDMs promotes an anti-inflammatory tissue-repair phenotype in these cells.

2021 ◽  
Author(s):  
Elya Abbaszadeh ◽  
Jalil Mehrzad ◽  
Seyed Mostafa Peighambari ◽  
Paniz Zarghami

Abstract Salmonella enterica subsp. enterica serovar Typhimurium is a gram-negative bacterium with the ability to infect a wide variety of hosts. Salmonella serovar Typhimurium (ST) infection in adult poultry usually results in an asymptomatic intestinal carriage while the infection in newly hatched chicks may lead to a severe clinical disease. Macrophages play an important role by limiting bacterial replication in submucosal tissues using several defense mechanisms. Subsequently, Salmonella strains have developed countermeasures to evade or subvert the host immune responses to their own benefit. We previously showed that ST challenge can greatly reduce the phagocytic capacity of chicken enriched peripheral blood monocytes. In the present study, we sought to provide a snapshot of the immune responses against ST challenge in chicken enriched peripheral blood monocytes by evaluating the transcriptional changes in inflammatory and anti-inflammatory cytokines, pattern recognition receptors, and some other immune-related molecules at mRNA level. Our results indicate that wildtype ST challenge in avian blood monocytes favors the differentiation of macrophages toward the alternatively activated M2-like cells through downregulation of inflammatory IL-1β and upregulation of anti-inflammatory IL-10 cytokines. Our result may partially explain how the bacterium modulate the immune response in professional phagocytes in order to survive in the hostile environment of host immune cells and further disseminate within the host.


1993 ◽  
Vol 2 (1) ◽  
pp. 49-52 ◽  
Author(s):  
E. F. Morand ◽  
D. Rickard ◽  
N. J. Goulding

The annexin lipocortin 1 is reported to mediate some anti-inflammatory effects of glucocorticoids, but the mechanisms of this mediation are incompletely understood. The involvement of lipocortin 1 in glucocorticoid inhibition of monocyte interleukin 1β (IL-1β) release has been investigated. Treatment of peripheral blood monocytes with 2 μg/ml lipopolysaccharide potently increased IL–1β release (p = 0.001) and dexamethasone (10−7M) significantly reduced both resting and stimulated IL-1β release (p = 0.009). A neutralizing monoclonal antibody to lipocortin 1 (0.5–50.0 μg/ml) was unable to inhibit this effect and recombinant lipocortin 1 (2 × 10−6M) and 188aa lipocortin 1 fragment (10−8−10−6M) had no effect. It is concluded that lipocortin 1 is not involved in the inhibition of monocyte IL-1β release by glucocorticoids.


2018 ◽  
Vol 46 (08) ◽  
pp. 1899-1914 ◽  
Author(s):  
Yin-Siew Lai ◽  
Renanda Baghaz Dzulhamdhani Surya Putra ◽  
Shin-Peir Aui ◽  
Ko-Tung Chang

Baicalin is the main active ingredient primary isolated from the Chinese herb, Scutellaria baicalensis Georgi. Although baicalin can induce M2 macrophage polarization, we still do not know the subtype of macrophages polarized by baicalin. In this study, we characterized that murine bone marrow derived macrophages induced by M-CSF can be further polarized into M2C phenotype by baicalin. The signatures of M2C macrophages for mRNA expression like interferon regulatory factor 4 (IRF4), interleukin-10 (IL-10), MERTK and PTX3 were up-regulated. Moreover, we observed the concomitantly decreasing of tumor necrosis factor alpha (TNF-[Formula: see text]), interferon regulatory factor 5 (IRF5), IL-6. In contrast, M2 macrophages polarized by IL-4 increased gene transcript of arginase-1 (Arg-1) and surface marker of CD206 indicates that their identity as M2A rather than M2C subtypes. Interestingly, the phagocytosis as well as efferocytosis activity were significantly enhanced in M2C macrophage polarized by baicalin and these capacities were associated with the expression of MERTK receptor. Finally, we conclude that baicalin induced M2C macrophages polarization with both elevations of efferocytosis and anti-inflammatory activity.


Diabetes Care ◽  
2012 ◽  
Vol 35 (12) ◽  
pp. 2631-2639 ◽  
Author(s):  
N. Satoh-Asahara ◽  
A. Shimatsu ◽  
Y. Sasaki ◽  
H. Nakaoka ◽  
A. Himeno ◽  
...  

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