Asthma is a chronic respiratory disease that manifests clinically as
a triad of cough, shortness of breath, and wheezing due to bronchial
hyperreactivity. Asthma is a major public health problem in
industrialized countries that affects an estimated 17 million adults and
4.8 million children in the US alone, accounting for significant
morbidity, school absenteeism, and lost work productivity. For
unexplained reasons, the incidence of asthma and Type 1 hypersensitivity
(atopy) is dramatically rising in Western countries, and now represents
the most common chronic disease of childhood. The etiology of asthma is
multifactorial, representing an interaction between genetic and
environmental factors. In all but the most severe cases, the clinical
pattern of asthma is one of periodic exacerbations of symptoms,
interspersed with periods of relative or complete inactivity of the
disease. Exacerbations of asthma are clearly linked to specific
environmental influences that accentuate the underlying process of
airway inflammation. The most prominent environmental factors include
exposure to aero-allergens, and particular types of respiratory viral
infections. The UTMB NIEHS Center Asthma Pathogenesis Core has made
significant progress in understanding the inflammatory mechanisms for
both of these environmental influences.
Research Highlights
Core Director and Members
Allan R. Brasier, M.D., Director,
Asthma Pathogenesis Research Core, Professor, Department of Internal
Medicine
Istvan Boldogh, DM&B, Ph.D., Member, Asthma Pathogenesis Research Core
and Director, Cell Biology Facility Core, NIEHS Center, Associate
Professor, Department of Microbiology and Immunology
Edward G. Brooks, M.D., Member, Asthma Pathogenesis Research Core and
Co-Director,COEP Division II: Asthma and Children's Environmental Health
Outreach, NIEHS Center, Associate Professor, Department of Pediatrics
William J. Calhoun,
M.D., Member, Asthma Pathogenesis Research Core, Professor,
Department of Internal Medicine
Antonella Casola, M.D., Member, Asthma Pathogenesis Research Core, NIEHS
Center, Assistant Professor, Department of Pediatrics
Teh-sheng Chan, M.D., Ph.D., Member, Asthma Pathogenesis Research Core, NIEHS Center, Professor, Department of Microbiology and Immunology
Roberto Garofalo, M.D., Member, Asthma Pathogenesis Research Core,
NIEHS Center, Professor, Department of Pediatrics
Randall M. Goldblum, M.D., Associate Director for Translational Research
and Co-Director, Asthma Pathogenesis Research Core, NIEHS Center,
Professor, Departments of Human Biological Chemistry and Genetics and
Pediatrics, Director, Child Health Research Center
Alex Kurosky, Ph.D., Member, Asthma Pathogenesis Research Core and
Director, Biomolecular Resource Facility Core, NIEHS Center, Professor,
Department of Human Biological Chemistry and Genetics
Sharon Petronella, Ph.D., Member, Asthma Pathogenesis Research Core and
Co-Director,COEP Division II: Asthma and Children's Environmental Health
Outreach, NIEHS Center, Assistant Professor, Department of Pediatrics
Sanjiv Sur, M.D., Member, Asthma Pathogenesis Research Core, NIEHS
Center, Professor, Departments of Internal Medicine and Pediatrics
Key Words
Adenosine Deaminase, Aeroallergens, Airway Inflammation, Asthma, Asthma
Epidemiology, Chemokines, Nuclear Factor-kappaB (NF-kappaB), Oxidative
Stress, Pollen, Respiratory Syncytial Virus
2005 Publications
Ameredes BT, Calhoun WJ.
2005 Jul. Modulation of GM-CSF release by enantiomers of beta-agonists
in human airway smooth muscle. J Allergy Clin Immunol. 116(1):65-72.
Ameredes BT, Sethi JM, Liu HL, Choi AM, Calhoun WJ.
2005 May. Enhanced nitric oxide production associated with airway
hyporesponsiveness in the absence of IL-10.
Am J Physiol Lung Cell Mol Physiol. 288(5):L868-73.
Ameredes BT, Zamora R, Sethi JM, Liu HL, Kohut LK, Gligonic AL, Choi AM, Calhoun WJ.
2005 Jul 15. Alterations in nitric oxide and cytokine production with
airway inflammation in the absence of IL-10. J Immunol.;175(2):1206-13.
Bacsi A, Choudhury BK, Dharajiya N, Sur S, and Boldogh I.
2005 Oct 1. Impact of pollen-mediated oxidative stress on hypersensitivity reactions and
lat-phase inflammation in allergic conjunctivitis. J. Allergy Clinical
Immunology, 116:836-843.
Bacsi A, Stanton GJ, Hughes TK, Kruzel M and Boldogh I. 2005 Nov
1. Colostrinin-driven neurite outgrowth requires p53 activation in PC12
cells. Cellular and Molecular Neurobiology, 25(7): 1123-1139.
Boldogh I, Bacsi A, Choudhury BK, Dharajiya N, Alam R, Hazra TK, Mitra S, Goldblum RM and Sur S. 2005.
ROS generated by pollen NADPH oxidase provide a signal that augments
antigen-induced allergic airway inflammation. J. Clin.
Invest.(115):2169-79.
Choudhary S, Boldogh I, Garofalo R, Jamaluddin M, Brasier AR.
2005 Jul 1. Respiratory syncytial virus influences NF-kappaB-dependent gene
expression through a novel pathway involving MAP3K14/NIK expression and
nuclear complex formation with NF-kappaB2. Journal of Virology
79:8948-8959.
Comhair SA, Xu W, Ghosh S, Thunnissen FB, Almasan A, Calhoun WJ,
Janocha AJ, Zheng L, Hazen SL, Erzurum SC. 2005 Mar. Superoxide
dismutase inactivation in pathophysiology of asthmatic airway remodeling
and reactivity.Am J Pathol. 166(3):663-74.
Czerwinski EW,
Midoro-Horiuti T, White MA, Brooks EJ, and Goldblum RM.
2005. Crystal structure of Jun a 1, the major cedar pollen allergen from
Juniperus ashei, reveals a parallel β-helical core. J. Biol. Chem.
280:3740-3746.
Erdely A, Kepka-Lenhart D, Clark M, Zeidler-Erdely P, Poljakovic M,
Calhoun WJ, Morris Jr SM. 2005 Oct 28. Inhibition of Phosphodiesterase 4 Amplifies
Cytokine-dependent Induction of Arginase in Macrophages. Am J Physiol
Lung Cell Mol Physiol.
Friesen JH, Ameredes BT, Calhoun WJ.
2005 Feb. Regarding Differential control of T(H)1 versus T(H)2 cell
responses by the combination of low-dose steroids with
beta(2)-adrenergic agonists.J Allergy Clin Immunol. 115(2):424.
Garofalo R P, Hintz KH, Hill V, Patti J, Ogra PL, and Welliver RC, Sr. 2005. A
comparison of epidemiologic and immunologic features of bronchiolitis
caused by influenza virus and respiratory syncytial virus.
J.Med.Virol. 75:282-289.
Guerrero-Plata A, Baron S, Poast JS, Adegboyega PA, Casola A,
and Garofalo RP. 2005. Activity and regulation of alpha
interferon in respiratory syncytial virus and human metapneumovirus
experimental infections. J Virol 79:10190-10199.
Guerrero-Plata A, Casola A, and Garofalo RP. 2005. Human
metapneumovirus induces a profile of lung cytokines distinct from that
of respiratory syncytial virus. J. Virol. 79:14992-14997.
Jamaluddin M, Choudhary S, Wang S, Casola A, Huda R, Garofalo
RP, Ray S, Brasier AR. 2005 Dec. Respiratory syncytial
virus-inducible BCL-3 expression antagonizes the STAT/IRF and NF-kappaB
signaling pathways by inducing histone deacetylase 1 recruitment to the
interleukin-8 promoter. J Virol. (24):15302-13.
Korenaga M, Chan T-s, Sun J, Weinman SA. 2005. Hepatitis C
virus core protein inhibits mitochondrial electron transport and
increases ROS production. J. Biol. Chem. 280:37481-37488.
Kudo T, Lu H, Wu JI, Graham DY, Casola A, Yamaoka Y. 2005.
Regulation of RANTES promoter activation in gastric epithelial cells
infected with H. pylori. Infection and Immunity 73(11):7602-12.
Liu T, Zaman W, Kaphalia BS, Ansari GAS, Garofalo RP, Casola A.
2005. RSV-induced prostaglandin E2 production occurs via cPLA2
activation: Role in viral replication. Virology 343:12-24.
Nightingale B, Dersch CM, Boos TL, Greiner E, Calhoun WJ, Jacobson AE, Rice KC,
Rothman RB. 2005 Aug. Studies of the biogenic amine
transporters. XI. Identification of a
1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine
(GBR12909) analog that allosterically modulates the serotonin
transporter.J Pharmacol Exp Ther.314(2):906-15.
Nowak DE, Tian B, Brasier AR. 2005.
Novel Two-Step Cross-linking method for Identification of NF-kB Gene Network by
Chromatin Immunoprecipitation. Biotechniques, 39(5): 715-725.
Paszek P, Lipniacki T, Brasier AR, Tian B, Nowak D, Kimmel M.
2005. Stochastic Effects of Multiple Regulators on Expression Profiles
in Eukaryotes. Journal of Theoretical Biology, 233:423-433.
Petronella S, Thomas R, Stone JA, Goldblum RM, and Brooks EG. 2005.
Clearing the air: a model for investigating indoor air quality in Texas
schools. J. Environmental Health. 67(10):35-42.
Ray S, Boldogh I, Brasier AR. 2005. STAT3 NH2-Terminal
Acetylation Is Activated By The Hepatic Acute-Phase Response And
Required for IL-6 Induction of Angiotensinogen. Gastroenterology,
129:1616-1632.
Rice JC, Peng T, Spence JS, Wang HQ, Goldblum RM, Corthesy B, and Nowicki BJ. 2005.
Pyelonephritic Escherichia coli expressing P fimbriae decrease
immune response of the mouse kidney. J Am Soc Nephrol 16:3583-3591.
Sun J, Tumurbaatar B, Jia J, Diao H, Bodola F, Lemon S, Tang W,
Bowen D.G., McCaughan G.W., Bertolino P, and Chan T-s. 2005.
Parenchymal expression of CD86/B7.2 contributes to hepatitis C
virus-related liver injury. J. Virol. 79:10730-10739.
Thaller E,
Moreno N, Petronella SA, Brooks EG. 2005.
Glutathione S-transferase polymorphisms are Linked to Asthma
and Low Breath Condensate pH. J Allergy Clin Immunol. 11(2):S310.
Tian B, Nowak D, Brasier AR. 2005. A TNF Induced Gene
Expression Program Under Oscillatory NF-kB Control. BMC Genomics,
6:137.
Tian B, Nowak D, Jamaluddin M, Wang S, Brasier AR. 2005.
Identification Of Direct Genomic Targets Downstream Of The NF-kB
Transcription Factor Mediating TNF Signaling. Journal of Biological
Chemistry, 280:17435-17448.
