Biomedical subjects

Jessica Jones

Publications and source records attributed to Jessica Jones.

4 recordsLinked to original sources

PubMed2005

Lyn-deficient mice develop severe, persistent asthma: Lyn is a critical negative regulator of Th2 immunity.

The etiology of asthma, a chronic inflammatory disorder of the airways, remains obscure, although T cells appear to be central disease mediators. Lyn tyrosine kinase has been implicated as both a facilitator and inhibitor of signaling pathways that play a role in allergic inflammation, although its role in asthma is unclear because Lyn is not expressed in T cells. We show in the present study that Lyn-/- mice develop a severe, persistent inflammatory asthma-like syndrome with lung eosinophilia, mast cell hyperdegranulation, intensified bronchospasm, hyper IgE, and Th2-polarizing dendritic cells. Dendritic cells from Lyn-/- mice have a more immature phenotype, exhibit defective inhibitory signaling pathways, produce less IL-12, and can transfer disease when adoptively transferred into wild-type recipients. Our results show that Lyn regulates the intensity and duration of multiple asthmatic traits and indicate that Lyn is an important negative regulator of Th2 immune responses.

Allergens↗

PubMed2005

Effect of short-term cigarette smoke exposure on body weight, appetite and brain neuropeptide Y in mice.

Although nicotinic receptors have been demonstrated in hypothalamic appetite-regulating areas and nicotine administration alters food intake and body weight in both animals and humans, the mechanisms underlying the effects of smoking on appetite circuits remain unclear. Conflicting effects of nicotine on the major orexigenic peptide, neuropeptide Y (NPY), have been observed in the brain, but the effects of smoking are unknown. Thus, we aimed to investigate how cigarette smoking affects body weight, food intake, plasma leptin concentration, hypothalamic NPY peptide, adipose mass and mRNA expression of uncoupling proteins (UCP), and tumor necrosis factor (TNF) alpha. Balb/C mice (8 weeks) were exposed to cigarette smoke (three cigarettes, three times a day for 4 consecutive days) or sham exposed. Body weight and food intake were recorded. Plasma leptin and brain NPY were measured by radioimmunoassay. UCPs and TNF alpha mRNA were measured by real-time PCR. Food intake dropped significantly from the first day of smoking, and weight loss became evident within 2 days. Brown fat and retroperitoneal white fat masses were significantly reduced, and plasma leptin concentration was decreased by 34%, in line with the decreased fat mass. NPY concentrations in hypothalamic subregions were similar between two groups. UCP1 mRNA was decreased in white fat and UCP3 mRNA increased in brown fat in smoking group. Short-term cigarette smoke exposure led to reduced body weight, food intake, and fat mass. The reduction in plasma leptin concentration may have been too modest to increase NPY production; alternatively, change in NPY or its function might have been offset by nicotine or other elements in cigarette smoke.

Adipose Tissue↗

PubMed2003

Innate immune responses to LPS in mouse lung are suppressed and reversed by neutralization of GM-CSF via repression of TLR-4.

The innate immune inflammatory response to lipopolysaccharide (LPS, an endotoxin) is essential for lung host defense against infection by gram-negative bacteria but is also implicated in the pathogenesis of some lung diseases. Studies on genetically altered mice implicate granulocyte-macrophage colony-stimulating factor (GM-CSF) in lung responses to LPS; however, the physiological effects of GM-CSF neutralization are poorly characterized. We performed detailed kinetic and dose-response analyses of the lung inflammation response to LPS in the presence of the specific GM-CSF-neutralizing antibody 22E9. LPS instilled into the lungs of BALB/c mice induced a dose-dependent inflammation comprised of intense neutrophilia, macrophage infiltration and proliferation, TNF-alpha and matrix metalloproteinase release, and macrophage inflammatory protein-2 induction. The neutralization of anti-GM-CSF in a dose-dependent fashion suppressed these inflammatory indexes by 85% when given before or after LPS or after repeat LPS challenges. Here we report for the first time that the physiological expression of Toll-like receptor-4 in lung is reduced by anti-GM-CSF. We observed that lower Toll-like receptor-4 expression correlated with a similar decline in peak TNF- levels in response to endotoxin. Consequently, sustained expression of key inflammatory mediators over 24 h was reduced. These data expand the understanding of the contribution of GM-CSF to innate immune responses in lung and suggest that blocking GM-CSF might benefit some lung diseases where LPS has been implicated in etiology.

Animals↗

PubMed2002

Future challenges in preparing for and responding to bioterrorism events.

The future success of our preparations for bioterrorism depends on many issues as presented in this article. If these issues are properly addressed, the resulting improvements in bioterrorism preparations will allow us to better deter and mitigate a bioterrorism incident and will also provide us with the added benefit of improvements in early detection, diagnosis, and treatment of natural disease outbreaks. Emergency physicians must take an active leading role in working with the various disciplines to produce a better-prepared community.

Bioterrorism↗