This study provides molecular epidemiological evidence that suggests in the present cohort that IL8 / CXCL8 -251 T allele, which is associated with higher production of IL8/CXCL8, is also associated with a higher risk of developing acute suppurative form of AP, whereas IL8 / CXCL8 -251 A allele, which is associated with lower production of IL8/CXCL8, is associated with chronic nonsuppurative form of AP. This suggests a pivotal role for IL-8/CXCL8 in periapical disease because of its ability to induce chemotaxis and modulating the directed migration of neutrophils to the site of inflammation in response to microbial infection of pulp.
In this study, we investigated the association between single-nucleotide polymorphisms (SNPs) of the interleukin-4 (IL4), interleukin-4 receptor-α (IL4RA) and interleukin-10 (IL10) genes with the development of chagasic heart disease. This study included 260 patients from Colombia who were serologically positive for Trypanosoma cruzi antigens (cardiomyopathic, n=130; asymptomatic, n=130). Genotypes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism or sequence-specific primer methods. We found statistically significant differences in the distribution of the IL4RA +148 AA (P=0·025, OR=1·89, CI=1·04-3·43) genotype when comparing asymptomatic and symptomatic patients. No statistically significant differences in the genotype and allele frequency of IL4 and IL10 gene polymorphisms between symptomatic and asymptomatic patients were observed. Our experimental evidence suggests that the IL4RA +148 AA genotype has a weak association with the development of chagasic cardiomyopathy in the population under study.
Chagas' disease (CD) is caused by infection with the intracellular protozoan parasite, Trypanosoma cruzi, and is the major cause of cardiomyopathy and heart failure in endemic regions of Colombia and South America (Guhl 1999, WHO 2002. A wide clinical spectrum is observed in the chronic phase of CD, varying from a relatively benign indeterminate form to gastrointestinal compromise or chronic cardiomyopathy that is usually fatal. The fact that only 20-30% of the infected individuals develop cardiomyopathy suggests a differential set of physiopathologic events between infected individuals. Differences in the expression of genes related to the immune response may be involved. In humans there are studies addressing the relation between the major histocompatibility complex genes and CD (Nieto et al. 2000). In addition, the C3F allele has been proposed as a marker for the progression of cardiomyopathy (Messias-Reason et al. 2003). Cytokine and chemokine genes have been implicated in determining increased susceptibility and further development of chagasic heart disease (Calzada et al. 2001, Flórez et al. 2006, Zafra et al. 2007). Genetic susceptibility to T. cruzi infection and the development of cardiomyopathy is complex and heterogeneous and likely involves several genes. The toll-like receptor family (TLRs) is a major class of eukaryotic receptors for microbial pathogens associated molecular patterns (PAMPs) and endogenous ligands. When TLRs recognize PAMPs induce signals responsible for the activation of genes relevant to the host defence including inflammatory and adaptative immunerelated cytokines (Takeda et al. 2003). Some of the microbial components recognized by these receptors have been identified. TLR2 recognizes a variety of microbial components such as lipoproteins from various pathogens, and lipoarabinomannan from mycobacteria and zymosan from fungi, among others. TLR4 recognizes principally lipopolysaccharide from Gram-negative bacteria (Takeda & Akira 2005). In protozoa, Plasmodium falciparum glycosylphosphatidylinositol (GPI) was reported to induce signaling via both TLR-2 and TLR-4 (Krishnegowda et al. 2005). GPI anchors of T. cruzi are recognized by TLR2 ). In addition T. cruzi Tc52 released protein and glycoinositolphospholipid, stimulating murine macrophages via TLR2 and TLR4 (Ouassi et al. 2002, Oliveira et al. 2004. Unmethylated CpG motifs of T. cruzi DNA also stimulate macrophages, dendritic cells and B lymphocytes probably via TLR-9 (Shoda et al. 2001). Some reports have shown that TLR-2, TLR-4 and the related signalling pathway play an important role in the initial recognition of T. cruzi and may regulate the initial pro-inflammatory response during infection with the parasite but may also contribute to the severity of the disease (Almeida & Gazzinelli 2001).Genetic variations in TLR genes correlate with several infectious diseases (Schroder et al. 2005). Several single-nucleotide polymorphism (SNPs) have been described for the TLR2 and TLR4 genes. The TLR2 argin- 28 ine to glutamine subst...
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