Search

Background: For many years, African Dust Storms (ADE) has been thought to be associated with high prevalence of asthma in Puerto Rico (PR). Endotoxins (ENX) have been associated with ADE particulate matter (PM) and are known to promote pro-inflammatory responses in lung cells of susceptible individuals through the Toll-like receptor (TLR2/4) signaling pathways. Genetic variants are plausible contributors to such susceptibility. Therefore, we have evaluated a series of nine single nucleotide polymorphisms (SNPs) in TLR genes, which have been correlated positive and negatively to asthma prevalence and/or risk, in the Puerto Rican asthmatic population., Methods: The following SNPs were evaluated in 62 asthmatics and 61 controls through Taqman® Real Time PCR Assay: TLR4 (+896A/G, +1196C/T, -6687A/G); TLR2 (+596C/T, -16934 T/A, +399A/G, +1349C/T) and CD14 (-159C/T, +1188C/G). Genotypes were assessed for asthma association employing an odds ratio (OR) analysis., Results: Minor allele frequencies (n = 123) were determined for those variants as 0.07, 0.06, 0.35, 0.35, 0.37, 0.29, 0.04, 0.35 and 0.11, respectively. Two (+596C/T, +399A/G) TLR2 SNPs showed to be more represented in the asthmatic group by 89 % and 65 %, respectively. TLR4 SNP +896A/G analysis revealed only 1 G/G genotype (2 %) on the asthmatic group. The CD14 SNPs were similarly represented in the Puerto Rican population. Only the TLR2 +596 SNP was found to be significantly associated to asthma (OR = 3.24 for CT, 2.71 for TT) and particularly to females., Conclusions: The identification of TLR SNPs will reveal potential candidates for gene-environment interactions in Puerto Ricans. As far as we know this is the first study to evaluate this type of TLR gene polymorphisms in Puerto Rican asthmatics, contributing to the current knowledge in the Hispanic population.

African Dust Events (ADE) are a seasonal phenomenon that has been suggested to exacerbate respiratory and proinflammatory diseases in Puerto Rico (PR). Increases in PM10 concentration and the effects of biological endotoxins (ENX) are critical factors to consider during these storms. ENX promote proinflammatory responses in lungs of susceptible individuals through activation of the Toll-like receptors (TLR2/4) signaling pathways. The objective of the study was to evaluate the toxicological and proinflammatory responses stimulated by ADE PM10 ENX reaching PR using human bronchial epithelial cells. PM10 organic extracts from a rural and urban site in PR (March 2004) were obtained from ADE and non-ADE and compared. A retrospective data analysis (PM10 concentration, aerosol images, and pediatric asthma claims) was performed from 2000 to 2012 with particular emphasis in 2004 to classify PM samples. Urban extracts were highly toxic, proinflammatory (IL-6/IL-8 secretion), and induced higher TLR4 expression and NF-κB activation compared to rural extracts. ENX were found to contribute to cytotoxicity and inflammatory responses provoked by urban ADE PM10 exposure suggesting a synergistic potency of local and natural ENX incoming from ADE. The contribution of ADE PM10 ENX is valuable in order to understand interactions and action mechanisms of airborne pollutants as asthma triggers in PR.

Puerto Ricans have the highest prevalence, morbidity and mortality of asthma than any other ethnic group in the U.S. and can be triggered by different stimuli such as airborne Particle pollution (PM). PM transfers transition metals, including cooper, to the human airways generating reactive oxygen species (ROS). Metallothionein protein (MT1A) is a free radical scavenger expected to be induced in lung cells by PM exposure; however, this has never been proven nor demonstrated. The hypothesis involves the amounts of PM10 in 2004, which would be significantly higher in the urban sites during months of March and June, thereby increasing PM metal exposure and inducing MT1A gene at the urban site. PM10 filters for Urban (Guaynabo) and rural (Fajardo) site were provided by the PREQB. Organic extracts were prepared from filters by means of Soxhlet Extraction and heavy metals were determined using Atomic Absorption Spectrometry. BEAS-2B cells were cultured and exposed to PM10 during 4 hrs. RNA was isolated and relative mRNA levels of MT1A were determined by RT-PCR. Urban PM10 concentrations were 35 ug/m³ and 60ug/m³ for the months of March and June, respectively. Concentrations of copper for this urban PM10 were 29.6 ppm and 50.3 ppm, for March and June, respectively. Exposure to Cu leads to an MT1A expression in lung cells demonstrating its response to metal exposure. Cellular response for the mRNA expression of MT1A was greater in relative high inflammation markers than in PM10 samples. [ABSTRACT FROM AUTHOR]