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PubMed2026

Association of PCSK9 and CCL22 gene polymorphisms with myocardial infarction in a South Indian population.

Myocardial infarction (MI) remains a major global cause of morbidity and mortality, with a particularly high burden among individuals with type 2 diabetes mellitus (T2DM). Host genetic factors play a significant role in modulating individual susceptibility to MI by influencing lipid metabolism and immune-mediated inflammatory pathways. The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is a key regulator of cholesterol homeostasis, while C-C motif chemokine ligand 22 (CCL22) is involved in immune cell recruitment and vascular inflammation. In this study, we investigated the association of PCSK9 rs505151 and rs11591147 and CCL22 rs4359426 polymorphisms with MI risk in a South Indian population. This case-control study included 400 participants categorized into controls (n = 100), MI (n = 100), T2DM (n = 100), and MI with T2DM (n = 100). Significant differences in clinical and biochemical parameters, including lipid indices and cardiometabolic risk markers, were observed between groups (p < 0.05). Genetic analysis revealed a significant association between the PCSK9 rs505151 variant and MI susceptibility across allelic and genotypic distributions, with significant effects under dominant and recessive inheritance models. Multivariable logistic regression confirmed that the rs505151 risk genotype was independently associated with MI after adjustment for age, sex, body mass index, and smoking status. In contrast, PCSK9 rs11591147 was rare and showed no significant association. The CCL22 rs4359426 polymorphism showed limited evidence of association with MI, with a significant effect observed only under the dominant inheritance model. Furthermore, combined analysis using a genetic risk score suggested that cumulative genetic burden involving PCSK9 and CCL22 variants was associated with an increased risk of MI. Overall, our findings suggest that genetic variation in lipid-regulatory and immune-related pathways may contribute to MI susceptibility in South Indians. Further studies are warranted to validate these associations and clarify their biological and clinical relevance.

Humans↗

PubMed2006

Efalizumab, a reversible T-cell modulator for psoriasis.

The humanized monoclonal antibody (MAb) efalizumab (Raptiva) was developed to meet a longstanding need for specific, safe, and effective anti-psoriatic treatments. Efalizumab, which is directed at the lymphocyte surface protein LFA-1, prevents multiple interactions between T cells and other cell types. Here, we review the inflammatory pathway that drives the development of psoriasis, and we discuss several mechanisms by which efalizumab suppresses skin inflammation in psoriasis. Efalizumab reversibly increases circulating T-cell counts, as T cells--including pathogenic CD8 memory T cells that are prominent in psoriatic lesions-- are specifically restrained from leaving the bloodstream and entering the skin. Within two weeks of the onset of efalizumab treatment, cell surface and intracellular LFA-1 pools are substantially cleared by lysosomal degradation. Residual surface LFA-1 molecules remain saturated with bound efalizumab for some weeks following cessation of treatment. Efalizumab's pharmacodynamic properties are consistent with its profound and reversible beneficial effects on the histopathology of psoriatic skin.

Antibodies, Monoclonal↗

PubMed2026

Integrative Transcriptomic and Proteomic Profiling Identifies S100P as a Potential Functional Biomarker for Sessile Serrated Lesions.

BACKGROUND: Sessile serrated lesions (SSLs) account for 15% of colorectal cancers (CRCs) but detection remains difficult due to flat morphology, mucinous features, and subtle histology. AIMS: This study aimed to identify novel and functionally relevant biomarkers of SSLs using transcriptomic screening and multi-omics validation. METHODS: Paired SSL and normal mucosa specimens (n = 6) underwent RNA sequencing. Differentially expressed genes (DEGs) were filtered for membrane or secretory proteins and validated across TCGA and adenoma transcriptomes. Functional significance was assessed using CRISPR dependency profiling, proteotranscriptomic concordance, pharmacogenomic sensitivity, and connectivity map analysis. RESULTS: We identified 216 upregulated genes in SSLs, including 68 encoding secretory/membrane proteins that better discriminated SSLs from controls and were enriched for adhesion and neuronal signaling while suppressing TNFα-NFκB inflammatory pathways. Cross-cohort comparison revealed five overlapping candidates between SSLs and TCGA CMS1 tumors. Among them, S100P emerged as the primary biomarker candidate, showing consistent upregulation in SSLs and CMS1 tumors while remaining low in normal mucosa and conventional adenomas. TFF1 also showed RNA-level upregulation but appeared more context-dependent. S100P demonstrated strong RNA-protein concordance in CRC cell-line profiling, supporting its detectability as a biomarker candidate. Pharmacogenomic profiling of LS411N cells revealed marked sensitivity to SN-38 and fluoropyrimidines, consistent with serrated CRC vulnerabilities. Connectivity map analysis identified perturbations, including MAPK1 and histone acetyltransferase suppression, that may reverse parts of the SSL transcriptional program. CONCLUSION: These findings prioritize S100P as a promising biomarker candidate for SSLs that warrants further validation in larger cohorts and clinically applicable platforms.

Humans↗

PubMed2004

Pharmacologic management of chronic rhinosinusitis, alone or with nasal polyposis.

Patients with chronic rhinosinusitis (CRS) and chronic rhinosinusitis with nasal polyposis (CRSwNP) commonly present with nasal obstruction, nasal discharge, facial pressure/pain, and hyposmia of prolonged duration. Recent evidence suggests that, despite clinical similarities, CRS and CRSwNP are distinct entities with separate inflammatory pathways and cytokine profiles. Antibiotics and nasal steroids are the mainstay of treatment in CRS, whereas combination systemic and nasal steroids are the foundation of CRSwNP management. Allergy therapy may play a significant role in CRS, whereas antileukotriene therapy has demonstrated promise in CRSwNP. Although prolonged medical therapy is usually necessary with both disorders, surgery may also be required to relieve refractory symptoms, and to improve sinus aeration and nasal access for topical therapy.

Administration, Topical↗

PubMed2005

The evolving role of inflammation in obesity and the metabolic syndrome.

Advances in adipose tissue biology over the past 10 years have led to an improved understanding of the mechanisms linking obesity with the metabolic syndrome and other complications. Obesity is characterized by a chronic, systemic low-grade state of inflammation. Biomarkers of inflammation, such as the leukocyte count, tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and C-reactive protein, are increased in obesity, associated with insulin resistance, and predict the development of type 2 diabetes and cardiovascular disease. It is now clear that the adipocyte is an active participant in the generation of the inflammatory state in obesity. Adipocytes secrete a variety of cytokines, including IL-6 and TNF-alpha, that promote inflammation. Moreover, recent studies suggest that obesity is associated with an increase in adipose tissue macrophages, which also participate in the inflammatory process through the elaboration of cytokines. An improved understanding of the role of adipose tissue in the activation of inflammatory pathways may suggest novel treatment and prevention strategies aimed at reducing obesity-associated morbidities and mortality.

Arteriosclerosis↗

PubMed2026

Mechanisms of Hematopoietic Stem Cell Aging and Emerging Rejuvenation Strategies.

Hematopoietic stem cell (HSCs) aging is a complex biological process driven by both cell-intrinsic alterations and extrinsic cues from the bone marrow niche. Understanding these mechanisms is critical for developing therapies against aging-related hematopoietic disorders. This review synthesizes recent advances in the molecular mechanisms underlying HSCs aging, including microenvironmental aging, genomic instability, epigenetic dysregulation, mitochondrial dysfunction, and aberrant nuclear mechanotransduction. We summarize that the functional decline of HSCs during aging drives a compensatory expansion of the phenotypically defined stem cell pool, leading to an aberrant increase in cell number. We also highlight aging-associated HSCs heterogeneity, including CD150high and P-selectin-positive subsets that enrich for myeloid-biased or functionally compromised HSCs states while emphasizing that surface phenotype alone may not fully indicate functional rejuvenation. Finally, we discuss emerging rejuvenation strategies-including targeting myeloid-biased HSCs, modulating inflammatory pathways, and implementing epigenetic or metabolic interventions-supported by cutting-edge technologies such as single-cell multi-omics, gene editing, and computational modeling. These approaches hold promise for counteracting age-related hematopoietic decline and restoring immune competence.

Humans↗

PubMed2025

Phytocompounds of Honey mesquite (Prosopis glandulosa) and Lodhra (Symplocos racemosa) in the management of COVID-19 associated rheumatoid arthritis (CARA).

COVID-19 persists globally with profound social and economic consequences, and its complex interplay with other diseases makes it a syndemic. Rheumatoid arthritis (RA), a chronic autoimmune disorder, has shown increased incidence during the pandemic, with patients displaying higher susceptibility to COVID-19. This overlap prompted the hypothesis of 'COVID-19-associated rheumatoid arthritis (CARA)'. The present study explores phytocompounds with anti-inflammatory and immunomodulatory properties as potential CARA therapeutics. Compounds from Prosopis glandulosa and Symplocos racemosa, both used in traditional medicine, were evaluated through molecular docking and simulation studies. Six inflammatory targets relevant to RA and COVID-19 -interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), human leukocyte antigen DR4 (HLA-DR4), signal transducer and activator of transcription 4 (STAT4), and peptidyl arginine deiminase 4 (PAD4) were selected. Among the tested ligands, salidroside showed the strongest binding affinity, with energies of - 8.20 kcal/mol (IL-6), - 7.67 kcal/mol (TNF-α), - 8.53 kcal/mol (GM-CSF), - 8.80 kcal/mol (HLA-DR4), - 8.18 kcal/mol (STAT4), and - 7.91 kcal/mol (PAD4), indicating stable interactions. These findings suggest salidroside could modulate key inflammatory pathways and potentially reduce cytokine storms in COVID-19 patients. Existing RA and COVID-19 treatments often cause immunosuppression, increasing vulnerability to opportunistic infections (Datta et al in J Biomol Struct Dyn 41(8):3281-3294, 2022). Immunomodulatory phytocompounds like salidroside may offer safer, targeted alternatives without compromising immune defenses. However, this study is based on in silico analyses, and warrants in vitro and in vivo validation. Nevertheless, present work may represent an important step towards novel therapeutic strategies for COVID-19 Associated Rheumatoid Arthritis (CARA).

COVID-19↗

PubMed1990

Tryptic and chymotryptic proteases released by larvae of the blowfly, Lucilia cuprina.

Proteases released by larvae of the sheep blowfly have been suggested to have a primary role in wound formation and larval nutrition. Assays were carried out on two larval products to analyse the substrate specificity of these proteases, their abundance and approximate molecular weights. Tryptic and chymotryptic activities were found in both products though there were more chymotrypsin-like enzymes in products from 48 h cultures (CESP) than in product collected direct from 48 h larvae (LESP). Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gels incubated with azocasein showed plaques of major enzyme activity at molecular weights of 20,000 and 26,000 in LESP and at 20,000 in CESP, SDS-PAGE gels, when reacted with peptide substrates showed tryptic activity at 20,000 and 26,000 in LESP, whereas CESP showed only chymotryptic activity at 20,000 and higher molecular weights. The results suggest at least three enzymes, a trypsin and chymotrypsin in LESP, a chymotrypsin in CESP and a tryptic enzyme which is not stable to SDS-PAGE probably in both LESP and CESP. In addition, reactivity with elastase and plasmin substrates suggests the presence of enzymes with general effects on skin substrates and inflammatory pathways.

Animals↗

PubMed1994

New perspectives on rheumatoid arthritis.

Rheumatoid arthritis (RA) remains one of the most common, puzzling and poorly treated diseases of humans. However, a surge of interest in the biology of chronic inflammation and in the design of more-potent and specific inhibitors of pro-inflammatory pathways heralds an optimistic era for the treatment of RA. A recent symposium provided a multidisciplinary perspective on the current status of such studies.

Arthritis, Rheumatoid↗

PubMed1995

Inhibition of radiation-induced up-regulation of leukocyte adhesion to endothelial cells with the platelet-activating factor inhibitor, BN52021.

PURPOSE: The inflammatory process is likely involved in normal tissue damage after radiation exposure, yet few studies have directly evaluated the factors that might be involved in the regulation of inflammation after irradiation in vivo. We tested the hypothesis that platelet-activating factor, a neutrophil agonist synthesized by endothelial cells, is involved in the upregulation of radiation-induced leukocyte-endothelial cell interactions by using an inhibitor of its receptor, BN52021. METHODS AND MATERIALS: Fischer-344 rats with dorsal skin-fold window chambers were randomized to three experimental groups: control (sham irradiation); 6 Gy radiation; and 6 Gy + BN52021. BN52021 (0.5 mg/kg) was administered 5 min prior to 6 Gy radiation. Leukocytes were stained in vivo with i.v. acridine orange for visualization with fluorescent microscopy. Venous vessel diameters were measured and number of rolling leukocytes were counted per 30-s period. The number of adhering leukocytes per unit surface area was also determined. Differences among the three experimental groups for rolling and adhering leukocytes were analyzed using a mixed-effects linear model with vessel shear rate used as a covariate. Results are reported as means +/- standard errors. RESULTS: Irradiation caused upregulation of leukocyte rolling, as compared with sham-treated controls (p = 0.04): the BN compound in addition to radiation did not downregulate this effect. Irradiation also upregulated leukocyte adhesion (p < 0.001), but the addition of BN52021 prior to irradiation blocked this effect. The drug did not affect heart rate or blood pressure. CONCLUSIONS: These results support the hypothesis that radiation-induced upregulation of leukocyte adhesion is mediated by platelet-activating factor. These results are consistent with prior reports that platelet-activating factor is not involved in leukocyte rolling, which involves separate families of adhesion molecules from those that regulate adhesion. BN52021, a ginkolide, or other related drugs might provide a useful pharmacological means to prevent or ameliorate inflammatory pathways that are invoked after radiation exposure.

Animals↗

PubMed2005

Acupuncture and kidney disease.

Acupuncture as a complex therapeutic system has been used to treat a variety of diseases and pathological conditions. Although the exact mechanism(s) of acupuncture remains unknown, some evidence suggests a mechanism initially involving signal transduction through connective tissue, with secondary involvement of other systems including the nervous system. Acupuncture has become increasingly popular in the Western countries as a therapy for pain and several chronic disorders difficult to manage with conventional treatments. Acupuncture and acupuncture-like somatic nerve stimulation have been used in different kidney diseases and several complications related to them. The effect of acupuncture techniques in some kidney diseases is reviewed on the basis of clinical reports as well as mechanisms that may possibly explain the beneficial effects mediated by acupressure/acupuncture. The potential effect of acupressure techniques in renal inflammation and whether these effects could be mediated through the newly identified cholinergic anti-inflammatory pathway are discussed.

Acupuncture Therapy↗

PubMed2005

Inflammation and coronary artery disease.

Inflammation is now recognized as being pivotal in the pathogenesis of atherosclerosis. This review highlights key concepts in our current understanding of the role of inflammation in the initiation, progression, and complication of atherosclerosis. The role of various triggers and amplifiers and the innate and adaptive immunity in the cascade of inflammatory events are also presented. Progress in our understanding of the inflammatory pathways in atherosclerosis has provided further mechanistic insight into the clinical benefits of current medical therapy and may alter our future treatment and preventive strategies.

Coronary Artery Disease↗

PubMed2006

Diverse associations of microalbuminuria with C-reactive protein, interleukin-18 and soluble CD 40 ligand in male essential hypertensive subjects.

BACKGROUND: Microalbuminuria (MA) and low-grade inflammation constitute emerging markers of subclinical atherosclerosis. We investigated whether urinary albumin excretion, expressed as the albumin-to-creatinine ratio (ACR), is associated with high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-18, and soluble CD40 ligand (sCD40L), in hypertensive subjects. METHODS: The study population consisted of 108 nondiabetic male patients with newly diagnosed untreated stage I to II essential hypertension (aged 44.6 years, office blood pressure [BP] 148/95 mm Hg). According to ACR values determined as the average of two nonconsecutive overnight spot urine samples, subjects were divided into microalbuminurics (n = 28) (mean ACR = 30 to 300 mg/g) and normoalbuminurics (n = 80) (mean ACR <30 mg/g). RESULTS: Although microalbuminurics as compared to normoalbuminuric hypertensives had greater hs-CRP levels (2.55 +/- 1.18 v 1.45 +/- 0.52 mg/L, P < .0001), independently of confounding factors, these two groups did not differ regarding IL-18 and sCD40L values (P = not significant [NS] for both cases). In the entire population, ACR exhibited a positive correlation with hs-CRP (r = 0.623, P < .0001), whereas there was no association with both IL-18 and sCD40L (P = NS for both cases). When multiple linear regression analysis was performed, it was revealed that age, body mass index, office systolic BP, total cholesterol, and hs-CRP levels were significant independent predictors of the ACR (P < .05). CONCLUSIONS: In essential hypertensive subjects, MA is accompanied by elevated hs-CRP levels, but not by augmented IL-18 and sCD40L concentrations, suggesting activation of different inflammatory pathways in the progression of renal and cardiovascular atherosclerotic disease. The pathophysiologic mechanisms of these associations remain to be further elucidated in future studies.

Adult↗

PubMed2006

Crosstalk between thrombosis and inflammation in lung reperfusion injury.

BACKGROUND: Activation of extravascular coagulation has been reported in acute lung injury models of sepsis and acute respiratory distress syndrome. Thrombin, the main effector protease of extravascular coagulation, activates proinflammatory cell types, including macrophages, endothelial cells, and neutrophils, each of which participates in lung ischemia-reperfusion injury. We used hirudin, a potent, specific direct thrombin inhibitor, to define the role of thrombin in lung ischemia-reperfusion injury. METHODS: Rats were pretreated with hirudin 30 minutes before warm, in situ left lung ischemia and reperfusion. Multiple in vivo assessments of lung injury were determined, and mechanistic studies assessed transcriptional regulation early in reperfusion and proinflammatory protein secretion late in reperfusion. Immunohistochemistry localized thrombin activation. RESULTS: Thrombin localized to macrophages and endothelial and epithelial cells early in reperfusion. Hirudin significantly limited lung ischemia-reperfusion injury-induced derangements in vascular permeability and intraalveolar inflammatory cell sequestration, resulting in improved arterial oxygenation after ischemia and 4 hours of reperfusion. The protection was transcriptionally mediated by attenuated activator protein-1 and early growth response-1 transactivation, but not nuclear factor kappa B transactivation. This was associated with reduced chemokine, but not tumor necrosis factor alpha, secretion late in reperfusion. CONCLUSIONS: Thrombin promotes lung ischemia-reperfusion injury, as hirudin protected against experimental acute lung injury. Hirudin conferred protection through a mechanism independent of nuclear factor kappa B and tumor necrosis factor alpha, suggesting that its effects may be mediated by a parallel, synergistic inflammatory pathway through activator protein-1 and early growth response-1.

Animals↗

PubMed2006

Chronic intermittent hypoxia alters hypothalamic transcription of genes involved in metabolic regulation.

Epidemiological studies show that the obstructive sleep apnea syndrome (OSAS) is strongly associated with obesity, hypertension and diabetes, the three conditions characteristic of the metabolic syndrome. Since metabolic disorders usually involve altered homeostatic mechanisms both centrally and peripherally, it is likely that so it is in OSAS, but the underlying mechanisms remain largely unknown. We used an established rodent model to test whether chronic intermittent hypoxia (CIH) similar to that experienced by OSAS patients leads to distinct and relevant for metabolic regulation transcriptional changes in the posterior hypothalamus. Using quantitative reverse transcription-polymerase chain reaction, we found that rats exposed to CIH for 35 days (n=9) had twice higher levels of the adrenergic alpha2A receptor mRNA than the rats simultaneously submitted to a matching sham treatment (n=9). The mRNA levels of three members of the family of signal transducers and activators of transcription, STAT1, STAT3 and STAT5b, were also increased 2-4 times. The increases occurred only in the perifornical region, whereas no changes were detected in the ventromedial region comprising the ventromedial and arcuate nuclei or the dorsomedial region comprising the dorsomedial and paraventricular nuclei. These results show that, at least at the transcriptional level, CIH exerts a distinct and regionally selective central effect on the expression of selected mRNAs involved in metabolic regulation through adrenergic, leptinergic and inflammatory pathways.

Animals↗

PubMed2005

Transcriptomics applied to obesity and caloric restriction.

Caloric restriction still remains the most efficient way to promote weight loss. Deciphering the molecular basis of adaptation to energy restriction is critical for the tailoring of new therapeutic strategies. This review focuses on the recent input of gene profiling on adipose tissue in obesity pathogenesis and on the new insights on adaptations occurring during very low caloric diet (VLCD) in humans. Hypocaloric diets improve a wide range of metabolic parameters including lipolytic efficiency, insulin sensitivity, and inflammatory profile. In the subcutaneous white adipose tissue (scWAT) the VLCD induced a decrease in the mRNA levels for the antilipolytic alpha2-adrenergic receptor associated with changes in catecholamine-induced adipocyte lipolytic capacity. The improvement in insulin sensitivity was not associated with a change in subcutaneous adipose tissue adiponectin gene expression or in its plasma level, suggesting that adiponectin is not involved in the regulation of VLCD-induced improvement of insulin sensitivity and that there is a small contribution of subcutaneous adipose tissue to plasma adiponectin levels. Pangenomic microarray studies in human scWAT revealed that a panel of inflammatory markers and acute phase reactants were over expressed in obese compared to lean subjects. Caloric restriction improved the inflammatory profile of obese subjects through a decrease of pro-inflammatory factors and an increase of anti-inflammatory molecules. These genes were mostly expressed in the stroma vascular fraction of the adipose tissue. Specific cell-type isolation and immunohistochemistry demonstrated that monocyte/macrophage lineage cells were responsible for the expression of both mRNA and protein inflammatory markers. The acute phase proteins serum amyloid A was highly expressed in mature adipocytes from obese subjects. Caloric restriction decreased both serum amyloid mRNA and circulating levels. Obesity now clearly appears as chronic low-grade inflammation state. Modulation of the inflammatory pathways may represent new therapeutic targets for the treatment of obesity-related complications.

Adipose Tissue↗

PubMed2006

Interleukin-10 is not a critical regulator of infarct healing and left ventricular remodeling.

OBJECTIVE: Interleukin-10 (IL-10) exerts potent anti-inflammatory actions and modulates matrix metalloproteinase expression. We hypothesized that endogenous IL-10 may regulate infarct healing and left ventricular remodeling by promoting resolution of the post-infarction inflammatory response and by modulating extracellular matrix metabolism. METHODS: IL-10 null and wildtype (WT) mice underwent reperfused infarction protocols. We compared the healing response and remodeling-associated parameters between IL-10-/-and WT infarcts. In addition, we studied the effects of IL-10 on inflammatory gene synthesis by stimulated murine cardiac fibroblasts. RESULTS: Infarcted IL-10-/-mice exhibited comparable mortality rates with WT animals. Although IL-10-/-mice had higher peak tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1/CCL2 mRNA levels in the infarcted heart than WT mice, both groups demonstrated timely repression of pro-inflammatory cytokine and chemokine mRNA synthesis after 24 h of reperfusion and exhibited a similar time course of resolution of the neutrophil infiltrate. IL-10 gene disruption did not alter fibrous tissue deposition and dilative remodeling of the infarcted heart. Pre-incubation with IL-10 did not modulate the pro-inflammatory phenotype of TNF-alpha-stimulated cardiac fibroblasts, failing to inhibit chemokine mRNA synthesis. In contrast, transforming growth factor (TGF)-beta1 pre-incubation suppressed interferon-gamma-inducible protein (IP)-10/CXCL10 synthesis by cardiac fibroblasts exposed to TNF-alpha. CONCLUSIONS: IL-10 signaling plays a non-critical role in suppression of inflammatory mediators, resolution of the inflammatory response, and fibrous tissue deposition following myocardial infarction. This may be due to the relative selectivity of IL-10-mediated anti-inflammatory actions, with respect to cell type and stimulus. Resolution of post-infarction inflammation is likely to involve multiple overlapping regulatory mechanisms controlling various pro-inflammatory pathways activated in the infarcted myocardium.

Animals↗

PubMed2005

Necrosis is associated with IL-6 production but apoptosis is not.

Due to loss of cell membrane integrity, necrotic cells passively release several cytosolic factors that can activate antigen presenting cells and other immune cells. In contrast, cells dying by apoptosis do not induce an inflammatory response. Here we show that necrotic cell death induced by several stimuli, such as TNF, anti-Fas or dsRNA, coincides with NF-kappaB-and p38MAPK-mediated upregulation and secretion of the pro-inflammatory cytokine IL-6. This event is greatly reduced or absent in conditions of apoptotic cell death induced by the same stimuli. This demonstrates that besides the capacity of necrotic cells to induce an inflammatory response due to leakage of cellular contents, necrotic dying cells themselves are involved in the expression and secretion of inflammatory cytokines. Moreover, inhibition of NF-kappaB and p38MAPK activation does not affect necrotic cell death in all conditions tested. This suggests that the activation of inflammatory pathways is distinct from the activation of necrotic cell death sensu strictu.

Amino Acid Chloromethyl Ketones↗