The Indonesian Biomedical Journal

81-90

Authors: Anna Meiliana, Andi Wijaya

BACKGROUND: Obesity is now recognized as the main cause of the worldwide epidemic of type 2 diabetes. Obesity-associated chronic inflammation is a contributing key factor for type 2 diabetes and cardiovascular disease. Numbers of studies have clearly demonstrated that the immune system and metabolism are highly integrated. CONTENT: Macrophages are an essential component of innate immunity and play a central role in inflammation and host defense. Moreover, these cells have homeostatic functions beyond defense, including tissue remodeling in ontogenesis and orchestration of metabolic functions. Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to interferons (IFNs), toll-like receptor (TLR), or interleukin (IL)-4/IL-13 signals, macrophages undergo M1 (classical) or M2 (alternative) activation. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1, M2 or M2-like polarized activation. SUMMARY: In response to various signals, macrophages may undergo classical M1 activation (stimulated by TLR ligands and IFN-γ) or alternative M2 activation (stimulated by IL-4/IL-13); these states mirror the T helper (Th)1–Th2 polarization of T cells. Pathology is frequently associated with dynamic changes in macrophage activation, with classically activated M1 cells implicate in initiating and sustaining inflammation, meanwhile M2 or M2-like activated cells associated with resolution or smoldering chronic inflammation. Identification of the mechanisms and molecules that are associated with macrophage plasticity and polarized activation provides a basis for macrophage centered diagnostic and therapeutic strategies.

101-6

Authors: Ritawaty Ritawaty, Indriyanti Rafi Sukmawati, Ilhamjaya Patellongi, Ferry Sandra

ACKGROUND: Gamma glutamyltransferase (GGT) was reported recently to be associated with inflammation, oxidative stress and increased amino acid. However, role of GGT in insulin resistance pathomechanism is not exactly known. Therefore correlation of GGT with inflammation, oxidative stress and elevated amino acid, in men with central obesity need to be confirmed. METHODS: A cross-sectional study was designed. Men with central obesity were recruited and selected. Anthropometric parameters, creatinine, hs-CRP, fasting glucose, fasting insulin, glutathione peroxidase (GPx) activity, GGT, plasma total cysteine (tCys) and fatty liver were measured. Subjects were then divided in 4 groups based on waist circumference (WC) and fatty liver: Group I: WC ≤100 cm, without fatty liver; Group II: WC ≤100 cm, with fatty liver; Group III: WC >100 cm, without fatty liver; Group IV: WC >100 cm, with fatty liver. All biochemical characteristics in each group were then statistically analyzed. RESULTS: Seventy-two men with central obesity were selected. Numbers of subjects in each group were: Group I: n=33; Group II: n=5; Group III: n=17; Group IV: n=17. We found significant difference of HOMA-IR between Group I and IV, significant correlation between GGT and HOMAIR, and significant negative correlation between tCys with HOMA-IR in Group IV. CONCLUSION: GGT was significantly correlated with HOMA-IR in men with WC >100 cm and fatty liver. Further investigation with more subjects is necessary to determine clear GGT cut-off to distinguish subjects with fatty liver and insulin resistance.

115-20

Authors: Adriana Todingrante, Mansyur Arif, Uleng Bahrun, Ferry Sandra

BACKGROUND: There is a prevalence increase of overweight and obesity in Indonesia. Central obesity can lead a variety of chronic diseases through the inflammatory process. There are some markers for low-grade chronic inflammatory, such as cathepsin S, high sensitivity C-reactive protein (hs-CRP), interleukin-1- beta (IL-1β). To our current interest that central obesity can lead to various chronic diseases through the inflammatory process, we conducted a study to investigate correlation of Cathepsin S, hs-CRP, IL-1β in men with central obesity. METHODS: A cross-sectional study was conducted. Seventy-eight selected subjects were examined to collect anthropometric data and prepared for sample collection. Collected samples were processed for the following biochemical analyses: fasting glucose, high density lipoprotein (HDL)-cholesterol, triglyceride, serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), cathepsin S, hs-CRP, and IL-1β. Data distribution and variable correlation were then statistically analyzed. RESULTS: There were significant correlations between waist circumference (WC) and cathepsin S (p=0.030; r=0.214), hs-CRP and cathepsin S (p=0.007; r=0.276), triglyceride and IL-1β (p=0.019; r=-0.235), WC and systolic blood pressure (SBP) (p=0.003; r=-0.312), WC and fasting glucose (p=0.000; r=0.380), WC and body mass index (BMI) (p=0.000; r=0.708). CONCLUSION: Our study showed that cathepsin S was correlated with central obesity, suggesting that cathepsin S could be a potential inflammatory marker in central obesity in the future.

129-36

Authors: Wiwik Rositawati, Syakib Bakri, Gatot Susilo Lawrence, Andi Wijaya

BACKGROUND: Vascular calcification may be an important risk factor of cardiovascular disease in Chronic Kidney Disease (CKD). The pathobiology of vascular calcification in CKD is complex and involves some factors including inflammation, oxidative stress and balancing of calcification regulators. The aim of the study was to investigate the interaction between 8-isoprostane with calcification regulators such as matrix gla protein (MGP) and bone morphogenetic protein (BMP)-2 with vascular calciication in CKD. METHODS: A cross-sectional study was performed on 63 subjects undergoing haemodialysis maintenance for more than 3 months. Abdominal aortic calcification (AAC) was measured using a lateral abdominal X-ray for calcification in abdominal aorta, which is related to severity of calcific deposits at lumbar vertebral segment (L)1-L4. Serum levels of 8-isoprostane, MGP and BMP-2 were measured by enzyme-linked immunosorbent assay method. RESULTS: Results showed that 8-isoprostane levels were correlated with BMP-2 (r=0.266, p=0.018) and MGP levels (r=0.410, p≤0.001). MGP/BMP-2 levels ratio was correlated with AAC score (r=0.279, p=0.013). Subjects were then stratified into 3 groups based on AAC score: 0, 1-6 and ≥7. The highest mean of MGP levels was in AAC score 1-6 group, and the highest mean of 8-isoprostane levels was in AAC score ≥7. In the group of AAC score 0, 8-isoprostane levels were correlated with MGP levels (r=0.499, p=0.001) and MGP/BMP-2 levels ratio (r=0.291, p=0.034). In AAC score 1-6 group, 8-isoprostane levels were correlated with BMP-2 (r=0.661, p=0.005) and MGP levels (r=0.569, p=0.017). In AAC score ≥7 group, MGP levels were positively correlated with AAC score (r=0.608, p=0.041). With multivariate logistic regression analyses, we identified that increased MGP/BMP-2 levels ratio (OR=12.436; 95% CI=1.595-96.971) was an independent predictor in aortic calcification event. CONCLUSION: We concluded that regulators of calcification including calcification inhibitor and promoter related to oxidative stress, were associated with vascular calcification in CKD. MGP levels were increased in the early of calcification and MGP/BMP-2 levels ratio was a strong predictor for vascular calcification in CKD.