Retinoic acid promotes fibrinolysis and may regulate polyp formation.

Background: Patients with aspirin-exacerbated respiratory disease (AERD) regularly exhibit severe nasal polyposis. Studies suggest that chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by excessive fibrin deposition associated with a profound decrease in epithelial tissue plasminogen activator (tPA). Retinoids, including vitamin A and its active metabolite retinoic acid (RA), are necessary for maintaining epithelial function and well-known inducers of tPA in endothelial cells.

Glucocorticoids Inhibit Group 3 Innate Lymphocyte IL-22 Production.

Glucocorticoids (GCs) are commonly prescribed to patients with a variety of inflammatory disorders, including inflammatory bowel disease (IBD). GCs mediate their immunomodulatory effects through many different mechanisms and target multiple signaling pathways. The GC dexamethasone downmodulates innate and adaptive immune cell activation.

Bacillus anthracis lethal toxin negatively modulates ILC3 function through perturbation of IL-23-mediated MAPK signaling.

Bacillus anthracis, the causative agent of anthrax, secretes lethal toxin that down-regulates immune functions. Translocation of B. anthracis across mucosal epithelia is key for its dissemination and pathogenesis.

Age-related increased prevalence of asthma and nasal polyps in chronic rhinosinusitis and its association with altered IL-6 trans-signaling.

We report that S100 proteins were reduced in patients with chronic rhinosinusitis (CRS). S100A8/9, which is important in epithelial barrier function, was particularly decreased in elderly patients with CRS. Epithelial expression of S100A8/9 is partly regulated by the IL-6 trans-signaling pathway.

Increased expression of the epithelial anion transporter pendrin/SLC26A4 in nasal polyps of patients with chronic rhinosinusitis.

Background: Chronic rhinosinusitis (CRS) is a multifactorial disease of unknown cause characterized by sinonasal inflammation, increased mucus production, and defective mucociliary clearance. Expression of Pendrin, an epithelial anion transporter, is increased in asthma and chronic obstructive pulmonary disease. Pendrin increases mucus production and regulates mucociliary clearance.

A role for anti-BP180 autoantibodies in chronic rhinosinusitis.

Objectives/hypothesis: Chronic Rhinosinusitis (CRS) is accompanied by evidence of a vigorous adaptive immune response, and emerging studies demonstrate that some nasal polyps manifest a polyclonal autoantibody response. We previously found that antibodies against BP180, a component of the hemidesmosome complex and the dominant epitope in autoimmune bullous pemphigoid, were found at elevated levels in nasal polyp tissue. Given the critical role of hemidesmosomes in maintaining epithelial integrity, we sought to investigate the distribution of BP180 in nasal tissue and evaluate for evidence of systemic autoimmunity against this antigen in CRS.

IκBζ augments IL-12- and IL-18-mediated IFN-γ production in human NK cells.

Interferon-γ (IFN-γ) production by natural killer (NK) cells and cytotoxic lymphocytes is a key component of innate and adaptive immune responses. Because inhibitor of κB-ζ (IκBζ), a Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) inducible transcription factor, regulates IFN-γ production in KG-1 cells, we tested IκBζ's role in the classic lymphocyte pathway of IL-12/IL-18-induced IFN-γ. Upon stimulation with IL-12/IL-18, monocyte-depleted human peripheral blood lymphocytes expressed the 79-kDa form of IκBζ and released IFN-γ.

Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps.

Background: IL-6 activates T(H)17 cells and regulates the response of B lymphocytes and regulatory T cells. The IL-6 receptor and the membrane protein, glycoprotein 130 (gp130), form an active signaling complex that signals through signal transducer and activator of transcription 3 (STAT3) and other signaling molecules. Both the IL-6 receptor (IL-6R) and gp130 can be found in soluble forms that regulate the pathway.

MAIL regulates human monocyte IL-6 production.

IL-6 is a pleiotropic cytokine implicated in the pathogenesis of disorders such as sepsis and cancer. We noted that human monocytes are excellent producers of IL-6 as compared with monocyte-derived macrophages. Because macrophages from molecule containing ankyrin repeats induced by LPS (MAIL) knockout animals have suppressed IL-6 production, we hypothesized that regulation of MAIL is key to IL-6 production in humans and may explain the differences between human monocytes and macrophages.

A novel role for IkappaBzeta in the regulation of IFNgamma production.

IkappaBzeta is a novel member of the IkappaB family of NFkappaB regulators, which modulates NFkappaB activity in the nucleus, rather than controlling its nuclear translocation. IkappaBzeta is specifically induced by IL-1beta and several TLR ligands and positively regulates NFkappaB-mediated transcription of genes such as IL-6 and NGAL as an NFkappaB binding co-factor. We recently reported that the IL-1 family cytokines, IL-1beta and IL-18, strongly synergize with TNFalpha for IFNgamma production in KG-1 cells, whereas the same cytokines alone have minimal effects on IFNgamma production.

Pyrin critical to macrophage IL-1beta response to Francisella challenge.

Relative to monocytes, human macrophages are deficient in their ability to process and release IL-1beta. In an effort to explain this difference, we used a model of IL-1beta processing and release that is dependent upon bacterial escape into the cytosol. Fresh human blood monocytes were compared with monocyte-derived macrophages (MDM) for their IL-1beta release in response to challenge with Francisella novicida.

Pyrin levels in human monocytes and monocyte-derived macrophages regulate IL-1beta processing and release.

Macrophages and their precursors, monocytes, are key cells involved in the innate immune response. Although both monocytes and macrophages produce caspase-1, the key enzyme responsible for pro-IL-1beta processing; macrophages are limited in their ability to activate the enzyme and release functional IL-1beta. In this context, because mutations in the pyrin gene (MEFV) cause the inflammatory disorder familial Mediterranean fever, pyrin is believed to regulate IL-1beta processing.