Plasma levels of TGF-β1 in homeostasis of the inflammation in sickle cell disease

Abstract

Sickle cell disease (SCD) represents a chronic inflammatory condition with complications triggered by the polymerization of hemoglobin S (Hb S), resulting in a series of cellular interactions mediated by inflammatory cytokines, as the transforming growth factor beta (TGF-β), which plays an important role in inflammation resolution. This study assessed the relation between SCD inflammation and the plasma concentration of TGF-β1, and also checked the influence of the presence of -509C/T polymorphism in TGFB1 gene on TGF-β1 plasma values. The plasma levels of TGF-β1 were quantified by ELISA in 115 patients with SCD (genotypes SS, SD-Los Angeles, Sβ-thalassemia and SC) and in 58 individuals with no hemoglobinopathies (Hb AA), as the control group. The -509C/T polymorphism in TGFB1 gene was screened by PCR-RFLP. The correlation between TGF-β1 plasma levels and the inflammation was based on its association with the count of platelets, total white blood cells (WBC) and neutrophils in the peripheral blood. Patients with SCD showed plasma levels of TGF-β1 higher than the control group, especially the Hb SS genotype, followed by the group with Hb SD. Polymorphism investigation showed no interference in the values obtained for the cytokine in the groups evaluated. All SCD groups showed TGF-β1 levels positively correlated to the platelets and WBC counts. The original data obtained in this study for SCD support the involvement of TGF-β1 in regulating of the inflammatory response and suggest that this marker possibly may become a potential therapeutic target in the treatment of the disease.

Thrombo-inflammation in COVID-19 and Sickle Cell Disease: Two Faces of the Same Coin

“…Interestingly, platelets contain 40 to 100 times more TGF-β1 than other cells and rapidly release TGF-β1 upon activation [132]. This is consistent with the positive correlation between plasma TGF-β1 and platelet and white blood cell counts in patients with steady-state SCD [133,134]. Interestingly, early, untimely TGF-β responses in SARS-CoV-2 infection limit the antiviral function of natural killer (NK) cells [135].…”

“…Interestingly, early, untimely TGF-β responses in SARS-CoV-2 infection limit the antiviral function of natural killer (NK) cells [135]. Therefore, TGF-β has been proposed as a therapeutic target in both SCD and COVID-19 [133,135].…”

Single Nucleotide Polymorphisms at +191 and +292 of Galectin-3 Gene (LGALS3) Related to Lower GAL-3 Serum Levels Are Associated with Frequent Respiratory Tract Infection and Vaso-Occlusive Crisis in Children with Sickle Cell Anemia

“…Patients with SCA have a chronic inflammation, characterized by ischemic condition and recurrent reperfusion, leading to the generation of oxidative burst and endothelial activation, as well as upregulation of adhesion molecules [31–33]. Therefore, GAL-3 may be important to SS erythrocyte removal and adhesion inhibition of those sickled erythrocytes in postcapillary venules protecting from VOC processes [30].…”

Inflammatory mediators in sickle cell anaemia highlight the difference between steady state and crisis in paediatric patients

“…We found increased levels of LTB4, PGE2 and TGF‐β among steady state patients. These molecules have been previously associated with neutrophil chemotaxis and vascular endothelial cells activation, and were also correlated with leucocyte counts (Setty & Stuart, ; Monteiro et al , ; Torres et al , ). Cytokines are molecules responsible for the signalling mechanisms during immune response and we identified higher IL1β, IL6, IL10 and TNF‐α levels in crisis state SCA.…”