Samina Bashir

Macrophage polarization: the link between inflammation and related diseases

ObjectiveIn the present review, we try to critically evaluate the two faces of the macrophages and their roles in relation to gene alteration in some inflammatory conditions. The pros- and cons of each type of macrophage in immunologic outcomes are discussed.IntroductionIf “Diversity is the rule of nature”, macrophages have proven to be its obedient followers. A cell type that was classically considered to be activated by Interferon-γ, under the influence of TH-1 type of response and a well-accepted warrior of cellular immunity to the intracellular pathogens is not as simple as once considered. Past decade has revolutionized this notion with the advent of TH-2 influenced alternatively activated macrophages, now established as wound repairing and tissue regenerating.MethodsLiterature survey was done to present a detailed study on this macrophage dichotomy and its relevance to immune disorders via expression of some critical genes, nuclear factor kappa-light-chain-enhancer of activated B cells, peroxisome proliferator-activated receptors and SH2-containing inositol-5′-phosphatase 1, highly implicated in a myriad of immunological emergencies like inflammation, insulin resistance, wound healing, cancer, etc.ConclusionThe evaluation of macrophage dichotomy in these disorders may prove to be the first step towards the formulation of innovative therapeutic approaches.

Amelioration of obesity-associated inflammation and insulin resistance in c57bl/6 mice via macrophage polarization by fish oil supplementation

Enormous phenotypic plasticity makes macrophages the target cells in obesity-associated inflammatory diseases. Thus, nutritional components that polarize macrophages toward antiinflammatory phenotype can partially reverse inflammatory diseases like insulin resistance. In the present study, macrophage-polarizing and insulin-sensitizing properties of fish oil (FO) were evaluated in obese insulin-resistant c57bl/6 mice fed high-fat diet (HFD-IR) after oral supplementation with FO (4, 8 or 16mg/kg body weight) and compared to lean and HFD-IR mice. FO-supplemented HFD-IR mice exhibited reduced adiposity index, serum cholesterol and triglycerides and increased insulin sensitization and showed improved adipose tissue physiology under light and transmission electron microscopy. NF-κB/P65 expression showed a downward shift on FO supplementation. The surface marker of M1 macrophages (CD-86) and the TLR-4 expression reduced with the increased supplementation of FO. Expression of arginase 1, an important marker of M2 macrophages, increased in a dose-dependent manner in response to FO dosage, which was observed at protein level by the western blotting and at mRNA level by real-time PCR. The cytokine profile of adipose tissue macrophages showed a steep shift toward antiinflammatory ones (IL-4 and IL-10) from the inflammatory TNF-α, IFN-γ, IL-2 and IL-1β. Thus, macrophage polarization seems to be the plausible mechanism via which FO alleviates obesity-induced inflammation and insulin resistance.

Implication of protein tyrosine phosphatase SHP-1 in cancer-related signaling pathways

The altered expression of SHP-1 (SH2 domain-containing protein tyrosine phosphatase) as a consequence of promoter hypermethylation or mutations has evidently been linked to cancer development. The notion of being a cancer drug target is conceivable as SHP-1 negatively regulates cell cycle and inflammatory pathways which are an inevitable part of oncogenic transformation. In the present review, we try to critically analyze the role of SHP-1 in cancer progression via regulating the above mentioned pathways with the major emphasis on cell cycle components and JAK/STAT pathway, commencing with the SHP-1 biology in immune cell signaling. Lastly, we have provided the future directions for researchers to encourage SHP-1 as a prognostic marker and curative target for this debilitating disease called as cancer.

Partial Reversal of Obesity-Induced Insulin Resistance Owing to Anti-Inflammatory Immunomodulatory Potential of Flaxseed Oil

The present study was designed to assess the potential of supplementation of diet with Flaxseed (Linum usitatissimum, L.) oil (FXO), on obesity-related inflammation and reversal of obesity-induced insulin resistance. Swiss Albino mice, C57bl/6 mice and co-culture of 3T3-L1 adipocytes – RAW 264.7 macrophages to mimick obese adipose tissue environment were used for the study. Oral gavage of FXO at concentrations of 4, 8 or 16 mg/kg body weight (bwt) for 4 weeks or high-fat diet (HFD, 60% energy as fat) supplemented with dietary FXO (4, 8 or 16 mg/kg bwt) was given to the mice. FXO was characterised using gas chromatography – mass spectrometry. FXO supplemented HFD-fed mice (4 mg/kg bwt exhibited reduced adiposity index, serum glucose levels and triglycerides (8 and 16 mg/kg bwt) and improvement in insulin sensitisation (4, 8 and 16 mg/kg bwt) when compared with HFD mice. The co-culture showed a dose-dependent shift in cytokines towards anti-inflammatory (IL-4) state, with a decrease in pro-inflammatory TNF-α (p < 0.05). For immunomodulatory studies a dose-dependent increase (p < 0.05) was observed in antigen-specific levels of Th2 (IL-4) cytokine, serum anti-ova IgG1 and IgE levels. Suppression in anti-ova IgG2a, IgG2b, and IgG3 and antigen-specific Th1 cytokines like TNF-α and IFN-γ significantly (p < 0.05) was observed at 16 mg/kg bwt dosage. The results indicate that FXO exhibits an anti-inflammatory immunomodulatory potential and may partially relieve symptoms of obesity-associated insulin resistance.

Gross and histopathological alterations associated with cystic echinococcosis in small ruminants

Hydatidosis, an important parasitic zoonoses is a major public health as well as economic concern throughout the world. A total of 2100, sheep (2052) and goats (48), slaughtered or spontaneously dead, from various areas of Kashmir valley were screened for the presence of hydatidosis. Out of 2100 cases, 85 were positive for hydatidosis. The frequently infected organs were lungs and liver. The liver was observed to be the most frequently infected organ with relative prevalence of 61.17% followed by lungs (38.82%). The pulmonary cysts were more fertile (55%) compared to hepatic cysts (45%). Histopathologicallly, the cyst wall consisted of the inner germinal, middle lamellated/laminated, and outer fibrous layer. Inflammatory reaction around the cyst was variable and was characterized by an inner zone of loosely arranged fibroblasts infiltrated with mononuclear cells, followed by densely arranged fibroblasts along with mononuclear cells; and an outer layer of fibrous connective tissue. Fibroplasia and calcification were noted at places. In liver besides the cellular reaction against the expanding cyst, hepatocellular degeneration and cirrhosis were observed, the severity of which was inversely related to the distance from the cyst. The structural details of the protoscolices were clearly discernable.

Mineral pitch stimulates humoral, cellular and innate immune responses in mice

Abstract Context: Mineral pitch (MP), a traditional medicine, is proposed to boost immunity in conditions that suppress Th1 cytokines such as AIDS/HIV, tuberculosis, leishmaniasis and cancer. Objective: This study investigates the immunoregulatory mechanisms of MP in innate, humoral and cell-mediated immunity. Materials and methods: Mice given MP (100, 200, 300 or 400 mg/kg, orally) for 10 consecutive days were immunized intravenously with goat RBC or ovalbumin, and investigated for plaque-forming cells (PFC), hemagglutination titer, hypersensitivity response, lymphocyte proliferation and macrophage function. Results: MP increased PFC (330.2 versus 182.2/106 splenocytes) in mice immunized with goat RBC and elicited ovalbumin-specific IgG titer at 400 mg/kg. Increase in Th1 immunity was correlated with the increased level of IFN-γ (724 versus 470 pg/ml) and decreased IL-4 (96 versus 178 pg/ml). CD4+/CD3+ ratio and delayed-type hypersensitivity response also increased to, respectively, 20.62 ± 0.59 (versus 16.47 ± 0.72) and 1.59 ± 0.12 (versus 0.87 ± 0.10 mm) in MP-treated mice. MP increased lymphocyte proliferation (11.14 ± 0.60 versus 5.81 ± 0.40 SI) and macrophage phagocyte response (0.24 ± 0.02 versus 0.15 ± 0.009), expressed as absorbance at 570 nm, but decreased nitrite production (17.4 ± 1.10 versus 24.3 ± 1.30 µM/106 cells). We also observed an increased bone marrow cellularity (24.5 ± 1.10 versus 17.10 ± 0.70 cells/femur) and WBC count (12 667 ± 377 versus 9178 ± 213 cells/mm3) following MP treatment. There was no sign of toxicity at 400 mg/kg, 1/12th of reported LD50. Conclusion: MP elicits a dose-dependent Th1 immune response.

Balanced TH1 and TH2 immunopotentiating effects of silicates partly containing nanoparticles present in calcined serpentine.

Abstract Calcined Serpentine (CS) is used in various formulations of alternative systems of medicine as a tonic to vital organs and as an anti-inflammatory agent. The process of calcination or incineration is believed to render non-toxic, gently absorbable, adaptable and digestible properties to the mineral compounds. The present study characterized CS and also evaluated its immunostimulatory potential. CS was characterized by using transmission electron microscopy (TEM), X-ray powder diffraction, atomic absorption spectroscopy and CHNS analysis. The characterized CS was further evaluated for its immunomodulatory potential in Swiss mice. X-Ray diffraction analysis revealed that the CS contained silicates of magnesium, calcium and iron as major minerals. Elemental composition and heavy metal analyses showed a presence of various inorganic elements/heavy metals, albeit at levels well below daily permissive intake values. TEM analysis of the test CS revealed a presence of nano particles with an average size of 10–20 nm (≈ 26% of total material). Oral administration of CS to mice at 50, 75, 100 or 200 μg/kg body weight for 10 days led to enhanced levels of total IgG, IgG1, IgG2a and IgG2b in ovalbumin-immunized mice as well as ex vivo lymphocyte proliferation and levels of TH1 (IL-2, IFNγ) and TH2 (IL-4, IL-10) cytokines produced by their cultured splenocytes. Similarly, CS treatment resulted in enhanced delayed-type hypersensitivity responses in GRBC-primed hosts. CS also activated host peritoneal macrophages, as indicated by increases in phagocytic activity and in TLR-2, CD80 and CD86 expression. The CS did not affect liver, kidney and spleen histology. Taken together, the results indicated that absorbed CS was stimulatory of host cell-mediated immune responses. It is hypothesized for now that the immunomodulatory effect of CS may have been due, in part, to a presence of nanoparticles on the CS; further study is required to validate this viewpoint.

Pathological and histochemical studies of the effects of cystic echinococcosis in sheep

A total of 2100 sheep, slaughtered or spontaneously dead, from various areas of Kashmir valley were screened for the presence of hydatidosis. Out of 2100 cases, 85 were positive for hydatidosis. Histopathologicallly, the cyst wall consisted of the inner germinal, middle lamellated, and outer fibrous layer. Inflammatory reaction around the cyst was variable and was characterized by an inner zone of loosely arranged fibroblasts infiltrated with mononuclear cells and densely packed fibroblasts mixed with mononuclear cells; and an outer layer of concentrically packed fibrous connective tissue. Mast cell reaction was observed mainly in the bronchiolar, peribronchiolar, and inflammatory zones in the lungs; while in the liver, mast cells were noted in portal triads and bile ducts and were least evident in the vicinity of the cysts. Qualitative increase was observed for acid mucopolysaccharides in fibroblasts, inflammatory cells, and bronchial epithelium, especially hyperplastic epithelial cells. Masson’s trichrome revealed intense formation of collagen fibers in the pericystic connective tissue. The calcareous corpuscles of the protoscolices were distinct when stained with combined Alcian blue PAS and toluidine stains but were not visible when stained with H & E and Masson’s trichrome stains.