Cytokines and Adhesion Molecules in Allergic Rhinitis

This review summarizes our current knowledge of nasal allergic inflammation based on studies of cytokines, chemokines, and adhesion molecules in allergic rhinitis. The article also includes some aspects of viral rhinitis. Due to artificial or natural allergen exposure, an increase in the number of eosinophils and basophils, mast cells, IgE-positive cells, macrophages, monocyte-like cells, Langerhans cells, and activated T-cells can be observed within the mucosa and on the mucosal surface. Mediators are known to be released in response to allergens, but do not seem to be adequate to initiate the cell recruitment. After antigen challenge, the release of proinflammatory and regulatory cytokines could be demonstrated, and TH2-type cytokine mRNA upregulation in allergic mucosa has been shown. Proinflammatory cytokines initiate an adhesion cascade and activate T-cells that create an “atopic” cytokine environment within the tissue, which also may be linked to the long-term selective recruitment of eosinophils. However, the acute selective migration of eosinophils after allergen challenge is not fully understood, nor is the role of chemokines in allergic and viral rhinitis. Allergic rhinitis clearly represents an inflammatory reaction.

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Role of Glucose-Lowering Medications in Erectile Dysfunction

Journal of Clinical Medicine ◽

10.3390/jcm10112501 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2501

Author(s):

Angelo Cignarelli ◽

Valentina Annamaria Genchi ◽

Rossella D’Oria ◽

Fiorella Giordano ◽

Irene Caruso ◽

...

Keyword(s):

Erectile Dysfunction ◽

Current Knowledge ◽

Smooth Muscle Contractility ◽

Glucose Lowering ◽

Glycation End Products ◽

Altered Metabolism

Erectile dysfunction (ED) is a long-term complication of type 2 diabetes (T2D) widely known to affect the quality of life. Several aspects of altered metabolism in individuals with T2D may help to compromise the penile vasculature structure and functions, thus exacerbating the imbalance between smooth muscle contractility and relaxation. Among these, advanced glycation end-products and reactive oxygen species derived from a hyperglycaemic state are known to accelerate endothelial dysfunction by lowering nitric oxide bioavailability, the essential stimulus of relaxation. Although several studies have explained the pathogenetic mechanisms involved in the generation of erectile failure, few studies to date have described the efficacy of glucose-lowering medications in the restoration of normal sexual activity. Herein, we will present current knowledge about the main starters of the pathophysiology of diabetic ED and explore the role of different anti-diabetes therapies in the potential remission of ED, highlighting specific pathways whose activation or inhibition could be fundamental for sexual care in a diabetes setting.

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Gastric Hyperplasia and Increased Proliferative Responses of Lymphocytes in Mice Lacking the COOH-terminal Ankyrin Domain of NF-κB2

Journal of Experimental Medicine ◽

10.1084/jem.186.7.999 ◽

1997 ◽

Vol 186 (7) ◽

pp. 999-1014 ◽

Cited By ~ 128

Author(s):

Hideaki Ishikawa ◽

Daniel Carrasco ◽

Estefania Claudio ◽

Rolf-Peter Ryseck ◽

Rodrigo Bravo

Keyword(s):

T Cells ◽

Lymphocyte Proliferation ◽

Cytokine Production ◽

Cell Types ◽

Homozygous Deletion ◽

Binding Activity ◽

Activated T Cells ◽

Physiological Relevance

The nfkb2 gene encodes the p100 precursor which produces the p52 protein after proteolytic cleavage of its COOH-terminal domain. Although the p52 product can act as an alternative subunit of NF-κB, the p100 precursor is believed to function as an inhibitor of Rel/NF-κB activity by cytoplasmic retention of Rel/NF-κB complexes, like other members of the IκB family. However, the physiological relevance of the p100 precursor as an IκB molecule has not been understood. To assess the role of the precursor in vivo, we generated, by gene targeting, mice lacking p100 but still containing a functional p52 protein. Mice with a homozygous deletion of the COOH-terminal ankyrin repeats of NF-κB2 (p100−/−) had marked gastric hyperplasia, resulting in early postnatal death. p100−/− animals also presented histopathological alterations of hematopoietic tissues, enlarged lymph nodes, increased lymphocyte proliferation in response to several stimuli, and enhanced cytokine production in activated T cells. Dramatic induction of nuclear κB–binding activity composed of p52-containing complexes was found in all tissues examined and also in stimulated lymphocytes. Thus, the p100 precursor is essential for the proper regulation of p52-containing Rel/NF-κB complexes in various cell types and its absence cannot be efficiently compensated for by other IκB proteins.

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Role of regulatory T cells in long-term immune dysfunction associated with severe sepsis

Critical Care Medicine ◽

10.1097/ccm.0b013e3181e78ad0 ◽

2010 ◽

Vol 38 (8) ◽

pp. 1718-1725 ◽

Cited By ~ 60

Author(s):

Daniele C. Nascimento ◽

José C. Alves-Filho ◽

Fabiane Sônego ◽

Sandra Y. Fukada ◽

Marcelo S. Pereira ◽

...

Keyword(s):

T Cells ◽

Severe Sepsis ◽

Regulatory T Cells ◽

Immune Dysfunction

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Clinical Role of Soluble Adhesion Molecules During Immunotherapy for Perennial Allergic Rhinitis

Archives of Otolaryngology - Head and Neck Surgery ◽

10.1001/archotol.124.1.41 ◽

1998 ◽

Vol 124 (1) ◽

pp. 41 ◽

Cited By ~ 2

Author(s):

Yoshihiro Ohashi ◽

Yoshiaki Nakai ◽

Ayaki Tanaka ◽

Yasushi Kakinoki ◽

Yoshiharu Ohno ◽

...

Keyword(s):

Allergic Rhinitis ◽

Adhesion Molecules ◽

Perennial Allergic Rhinitis ◽

Clinical Role ◽

Soluble Adhesion Molecules

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Role of Superantigens in Allergic Inflammation: Their Relationship to Allergic Rhinitis, Chronic Rhinosinusitis, Asthma, and Atopic Dermatitis

American Journal of Rhinology and Allergy ◽

10.1177/1945892418801083 ◽

2018 ◽

Vol 32 (6) ◽

pp. 502-517 ◽

Cited By ~ 11

Author(s):

Nuray Bayar Muluk ◽

Fazilet Altın ◽

Cemal Cingi

Keyword(s):

T Cells ◽

Allergic Rhinitis ◽

Atopic Dermatitis ◽

Inflammatory Response ◽

Chronic Rhinosinusitis ◽

Inflammatory Responses ◽

Immunoglobulin E ◽

Severe Disease ◽

Allergic Inflammation ◽

Allergic Dermatitis

Objectives Our intention was to review all material published to date regarding superantigens (SAgs) and allergy from an otorhinolaryngological viewpoint to understand this association more clearly. Methods We identified all materials published mentioning both SAg and allergic rhinitis (AR), chronic sinusitis, asthma, and atopic dermatitis (AD) that are indexed on PubMed, Google, or the ProQuest Central databases. Results Staphylococcus aureus is a significant bacterial pathogen in humans and has the ability to produce enterotoxins with superantigenic features. The inflammatory response in allergy seen in both B cell and T cell may be attributed to SAgs. Sufferers of both allergic asthma with rhinitis and AR alone produce serological evidence of immunoglobulin E formation to SAgs produced by S. aureus. Perennial AR sufferers carry S. aureus more frequently and the presence of the organism within the nasal cavity may exacerbate perennial AR. SAg produced by S. aureus potentially worsens the asthmatic inflammatory response within the airway and may lead to the airways becoming hyperresponsive, as well as possibly activating T cells if asthmatic control is poor. Staphylococcal SAgs potentially increase the risk of developing chronic rhinosinusitis with nasal polyposis, additionally being a marker for more severe disease. If SAgs bring about chronic inflammatory responses in the nose and sinuses, then T cells excreting interferon-gamma may be a crucial mediator. In allergic dermatitis, S. aureus could be a key player in exacerbation of the condition. Even in younger pediatric patients with allergic dermatitis, allergic hypersensitivity to SAgs is frequent and may be a factor explaining how severe the condition becomes. Conclusion Just as SAgs are known to feature in many allergic conditions, they play their part in AR, chronic rhinosinusitis, asthma, and AD. Further research is required before the relationship between SAgs and allergy can be adequately explained.

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Virus-activated T cells regulate expression of adhesion molecules on endothelial cells in sites of infection

Journal of Neuroimmunology ◽

10.1016/0165-5728(95)00099-n ◽

1995 ◽

Vol 62 (1) ◽

pp. 35-42 ◽

Cited By ~ 30

Author(s):

Ole Marker ◽

Annika Scheynius ◽

Jan Pravsgaard Christensen ◽

Allan Randrup Thomsen

Keyword(s):

T Cells ◽

Endothelial Cells ◽

Adhesion Molecules ◽

Activated T Cells

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SHP-1 Acts as a Key Regulator of Alloresponses by Modulating LFA-1-Mediated Adhesion in Primary Murine T Cells

Molecular and Cellular Biology ◽

10.1128/mcb.00294-16 ◽

2016 ◽

Vol 36 (24) ◽

pp. 3113-3127 ◽

Cited By ~ 3

Author(s):

Martin G. Sauer ◽

Jessica Herbst ◽

Ulf Diekmann ◽

Christopher E. Rudd ◽

Christian Kardinal

Keyword(s):

T Cells ◽

T Cell ◽

Tyrosine Phosphatase ◽

Activated T Cells ◽

Sirna Knockdown ◽

Antigen Presenting ◽

Pharmaceutical Agents ◽

Interfering Rna ◽

Clinical Potential

The clinical potential of transplantation is often reduced by T cell-mediated alloresponses that cause graft rejection or graft-versus-host disease. Integrin-mediated adhesion between alloreactive T cells and antigen-presenting cells is essential for allorejection. The identity of the signaling events needed for the activation of integrins such as LFA-1 is poorly understood. Here, we identified a novel role of the protein tyrosine phosphatase SHP-1 in the regulation of murine LFA-1-mediated adhesion in an allograft setting. Upon alloactivation, SHP-1 activity is reduced, resulting in an increase in LFA-1 adhesion compared to that for syngeneically activated T cells. The importance of these differential activation properties was further indicated by small interfering RNA (siRNA) knockdown of SHP-1 in syngeneically and allogeneically stimulated T cells. Mechanistically, SHP-1 modulated the binding of SLP-76 to ADAP by dephosphorylation of the YDGI tyrosine motif of ADAP, a known docking site for the Src family kinase Fyn. This novel key role of SHP-1 in the regulation of LFA-1-mediated adhesion may provide a new insight into T cell-mediated alloresponses and may pave the way to the development of new immunosuppressive pharmaceutical agents.

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Abstract 4008: PSGL-1-Expressing CD4 T Cells are Enriched in Culprit Coronary Artery Lesion of Acute Coronary Syndrome

Circulation ◽

10.1161/circ.118.suppl_18.s_817-b ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Keiko Gomita ◽

Kayoko Sato ◽

Kazutaka Kitamura ◽

Nobuhisa Hagiwara

Keyword(s):

T Cells ◽

Acute Coronary Syndrome ◽

Coronary Artery ◽

Adhesion Molecules ◽

Peripheral Blood ◽

Cd4 T Cells ◽

Coronary Artery Lesion ◽

Plaque Instability ◽

Coronary Syndrome

Background: Recently, several evidences on the crucial role of adhesion molecules in the development of atherosclerosis and plaque instability have been reported. While expression of VCAM-1, ICAM-1 and L-selectin has been consistently observed in atherosclerotic plaques it is still uncertain how adhesion molecules on T cells contribute to the incidence of acute coronary syndrome (ACS). In this study, we examined whether adhesion molecules on T cells in ACS have a significant role in the plaque stability and prone to cause ACS. Methods and Results: Fresh CD4 T cells were isolated from the peripheral blood of 76 ACS patients (AMI=35, UAP=41) and 74 age-matched controls (NC). CD69, an activation marker of T cells, was strongly expressed on CD4 T cells from ACS than from NC by FACS (P<0.0001). CD4 T cells from ACS highly expressed p-selectin glycoprotein ligand-1 (PSGL-1) and integrin β (CD18), but not L-selectin by FACS (P < 0.03, P < 0.01, n.s., respectively). Soluble PSGL-1 (sPSGL-1) levels in plasma were lower in ACS patients than in NC (P=0.0001), which correlated negatively with the PSGL-1 expression on CD4 T cells (R=0.405, P<0.02). We further investigated the thrombus-aspirating device samples (n=14) and fresh CD4 T cells derived from both the coronary artery and peripheral blood from the each same patient with ACS. CD4 T cells from the coronary artery strongly expressed PSGL-1 (P<0.002), but not integrin β (CD18) and L-selectin by FACS. Finally, PSGL-1 was expressed on T cells, but not on CD68 positive macrophage, MPO positive neutrophil, or CD41 positive platelets in the thrombus-aspirating device samples. Conclusions: From these results, we demonstrated that PSGL-1-expressing CD4 T cells are enriched in the culprit coronary artery lesion of ACS, contributing to the acceleration of plaque instability and occurrence of ACS.

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HIV-specific T-cell Responses and Generalized Activation in HIV-1 Infected Long-term Non-progressors and Progressors from South India

Current HIV Research ◽

10.2174/1570162x17666181212122607 ◽

2019 ◽

Vol 16 (4) ◽

pp. 302-314

Author(s):

Chinnambedu Ravichandran Swathirajan ◽

Ramachandran Vignesh ◽

Greer Waldrop ◽

Uma Shanmugasundaram ◽

Pannerselvam Nandagopal ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Cd4 T Cell ◽

Cell Responses ◽

Activation Rates ◽

Hiv 1

Background:Anti-viral cytokine expressions by cytotoxic T-cells and lower activation rates have been reported to correlate with suppressed HIV replication in long-term non-progressors (LTNP). Immune mechanisms underlying disease non-progression in LTNP might vary with HIV-1 subtype and geographical locations.Objective:This study evaluates cytokine expression and T-cells activation in relation to disease non-progression in LTNP.Methods:HIV-1 Subtype C infected LTNP (n=20) and progressors (n=15) were enrolled and flowcytometry assays were performed to study HIV-specific CD8 T-cells expressing IL-2, IFN-γ, TNF-α and MIP-1β against gag and env peptides. CD4+ T-cell activation was evaluated by surface expression of HLADR and CD38.Results:Proportions of cytokines studied did not differ significantly between LTNP and progressors, while contrasting correlations with disease progression markers were observed in LTNP. CD4+ T-cell activation rates were significantly lower in LTNP compared to progressors which indicate the potential role of T-cell activation rates in disease non-progression in LTNP.Conclusion:LTNP and progressors showed similar CD8+ T-cell responses, but final conclusions can be drawn only by comparing multiple immune factors in larger LTNP cohort with HIV-1 infected individuals at various levels of disease progression. A possible role of HIV-1 subtype variation and ethnic differences in addition to host-genetic and viral factors cannot be ruled out.

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