ABSTRACT
CO2 is a physiological gas normally produced in the body during aerobic respiration. Hypercapnia (elevated blood pCO2 >≈50 mm Hg) is a feature of several lung pathologies, e.g. chronic obstructive pulmonary disease. Hypercapnia is associated with increased susceptibility to bacterial infections and suppression of inflammatory signaling. The NF-κB pathway has been implicated in these effects; however, the molecular mechanisms underpinning cellular sensitivity of the NF-κB pathway to CO2 are not fully elucidated. Here, we identify several novel CO2-dependent changes in the NF-κB pathway. NF-κB family members p100 and RelB translocate to the nucleus in response to CO2 A cohort of RelB protein-protein interactions (e.g. with Raf-1 and IκBα) are altered by CO2 exposure, although others are maintained (e.g. with p100). RelB is processed by CO2 in a manner dependent on a key C-terminal domain located in its transactivation domain. Loss of the RelB transactivation domain alters NF-κB-dependent transcriptional activity, and loss of p100 alters sensitivity of RelB to CO2 Thus, we provide molecular insight into the CO2 sensitivity of the NF-κB pathway and implicate altered RelB/p100-dependent signaling in the CO2-dependent regulation of inflammatory signaling.
Subject(s)
Carbon Dioxide/immunology , Hypercapnia/immunology , NF-kappa B p52 Subunit/immunology , Signal Transduction/immunology , Transcription Factor RelB/immunology , A549 Cells , Animals , Humans , Hypercapnia/genetics , Hypercapnia/pathology , Mice , NF-kappa B p52 Subunit/genetics , Protein Domains , Signal Transduction/genetics , Transcription Factor RelB/genetics , Transcription, Genetic/genetics , Transcription, Genetic/immunologyABSTRACT
We studied the feasibility of using halloysite clay nanotubes (HNTs) and carboxyl-functionalised multi-walled carbon nanotubes (COOH-MWCNTs) as antigen carriers to improve immune responses against a recombinant LipL32 protein (rLipL32). Immunisation using the HNTs or COOH-MWCNTs significantly increased the rLipL32-specific IgG antibody titres (p < 0.05) of Golden Syrian hamsters. None of the vaccines tested conferred protection against a challenge using a virulent Leptospira interrogans strain. These results demonstrated that nanotubes can be used as antigen carriers for delivery in hosts and the induction of a humoral immune response against purified leptospiral antigens used in subunit vaccine preparations.
Subject(s)
Aluminum Silicates/immunology , Bacterial Outer Membrane Proteins/immunology , Bacterial Vaccines/immunology , Immunoglobulin G/analysis , Leptospira interrogans/immunology , Lipoproteins/immunology , Nanotubes, Carbon , Animals , Antigens/administration & dosage , Antigens, Bacterial/administration & dosage , Antigens, Bacterial/immunology , Carbon Dioxide/immunology , Clay , Cricetinae , Feasibility Studies , Immunity, Humoral/immunology , Leptospira interrogans/classification , Mesocricetus , Recombinant Proteins/administration & dosage , Recombinant Proteins/immunologyABSTRACT
Human activities are resulting in increases in atmospheric greenhouse gases, such as carbon dioxide, and changes in global climate. These, in turn, are likely to have had, and will continue to have, impacts on human health. While such impacts have received increasing attention in recent years, the impacts of climate change on aeroallergens and related allergic diseases have been somewhat neglected. Despite this, a number of studies have revealed potential impacts of climate change on aeroallergens that may have enormous clinical and public health significance. The purpose of this review is to synthesize this work and to outline a number of research challenges in this area. There is now considerable evidence to suggest that climate change will have, and has already had, impacts on aeroallergens. These include impacts on pollen amount, pollen allergenicity, pollen season, plant and pollen distribution, and other plant attributes. There is also some evidence of impacts on other aeroallergens, such as mould spores. There are many research challenges along the road to a more complete understanding of the impacts of climate change on aeroallergens and allergic diseases such as asthma and hayfever. It is important that public health authorities and allergy practitioners be aware of these changes in the environment, and that research scientists embrace the challenges that face further work in this area.
Subject(s)
Allergens/immunology , Climate , Pollen/immunology , Air , Carbon Dioxide/immunology , Fungi/immunology , Humans , Hypersensitivity/immunology , Plant Development , SeasonsSubject(s)
Cholecystectomy, Laparoscopic , Insufflation/methods , C-Reactive Protein/immunology , C-Reactive Protein/metabolism , Carbon Dioxide/immunology , Carbon Dioxide/metabolism , HLA-DR Antigens/immunology , HLA-DR Antigens/metabolism , Helium/immunology , Helium/metabolism , Humans , Inflammation/prevention & control , Statistics, Nonparametric , Treatment OutcomeABSTRACT
Respiratory sensitivity was evaluated in 10 patients with schizophrenia and 10 normal control subjects utilizing a rebreathing system and measurements of the changes in the mouth occlusion pressure in 100 ms and ventilation in response to the increase in end-tidal PCO2 (PetCO2). Although ventilation response was similar in both groups, we noted that the occlusion pressure response was more variable (coefficient of variability, CV = 17.5%) and the correlation coefficient (r = 0.75 +/- 0.13) lower in the patients with schizophrenia compared to controls (CV = 4.6%; r = 0.90 +/- 0.04). Apnea threshold was also lower in patients with schizophrenia (29.03 +/- 12.73 Torr, mean +/- SD) compared to controls (39.5 +/- 4.5 Torr). Furthermore, schizophrenia patients showed a significant positive and negative correlation between occlusion pressure response and age (r = 0.73; p less than 0.001) and estimated duration of schizophrenia (r = 0.65; p less than 0.05). We conclude that the apnea threshold is lower and the respiratory sensitivity to CO2 is more variable in patients with schizophrenia compared to normal subjects.
Subject(s)
Carbon Dioxide/immunology , Schizophrenia/immunology , Adult , Aging/physiology , Breath Tests , Humans , Middle Aged , Mouth , Pressure , Respiratory Hypersensitivity/immunologyABSTRACT
The influence of the presence of a terminal COOH or CONH2 on the antigenic characters of synthetic immunogenic peptides has been studied on a streptococcal synthetic vaccine model. The obtained results show that when a peptide amide is used, the antibodies raised specifically against the amide group recognize neither free COOH nor the parent protein. The carboxamide group is thus unsuitable as was postulated for raising antibodies which recognize the peptide bond.