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Effect of eosinophils activated with Alternaria on the production of extracellular matrix from nasal

osisposis

Senior Member
Messages
389
Effect of eosinophils activated with Alternaria on the production of extracellular matrix from nasal fibroblasts.

http://www.ncbi.nlm.nih.gov/pubmed/27156749

Alternaria Induces Production of Thymic Stromal Lymphopoietin in Nasal Fibroblasts Through Toll-like Receptor 2.
http://www.ncbi.nlm.nih.gov/pubmed/26540503

full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695410/

TSLP expression is increased in allergic rhinitis and nasal polyps, and the TSLP expression level is significantly greater in nasal polys, irrespective of whether nasal polyps are atopic or non-atopic, than in the allergic rhinitis.4,5 The immunoreactivity for TSLP has been detected in nasal epithelial cells, endothelial cells, fibroblasts, and inflammatory cells in nasal polyps.5 Fibroblasts are major structural components of nasal mucosa, which confer mechanical strength by providing a supporting framework of extracellular matrix and play an important role as a source of chemical mediators in the initiation and amplification of inflammatory reaction.6 Nasal polyp fibroblasts produce TSLP in response to stimulation by TNF-α and IL-1β via distinct signal transduction pathways, including NF-κB.7


TLR2 and TLR5 mRNA expressions were significantly increased by the fungi.
TLRs are essential receptors for the recognition of pathogenic microorganisms and activation of the immune system. The activation of TLRs allows primary defensive immune mechanisms to be initiated locally, which initiate communication of the presence of pathogens to the adaptive immune system.14 Eleven TLR members have been identified in human, and they are triggered by conserved molecular structures expressed by bacteria, virus, and fungi. TLR2, TLR4, and TLR9 are the main TLRs involved in sensing fungal components.15 TLR2 and TLR4 mRNAs have been found to be expressed in nasal epithelial cells and these 2 genes have been reported to be significantly higher in chronic rhinosinusitis.16 Fungal antigens induce the production of IL-6 and IL-12 from dendritic cells via TLR2 and TLR4.16 Alternaria and Aspergillus can enhance TLR2, TLR3, and TLR4 mRNA expression from nasal epithelial cells, and TLR4 is thought to contribute to the production of chemical mediators.9 In nasal fibroblasts, Alternaria and Aspergillus enhanced the expression of TLR2 and TLR5 mRNAs. TLR2 mediates cell responses to lipoproteins and lipoteichoic acid from gram-positive bacteria and some gram-negative bacteria and fungi. TLR2 has been shown to functionally collaborate with distinct types of receptors such as dectin-1, a lectin family receptor for the fungal cell wall component β-glucan.17 TLR5 plays an important role in microbial recognition at the mucosal surface by responses to bacterial flagella and induction of inflammatory cytokine production.
However, TLR5 is not commonly associated with fungal infection. Alternaira and Aspergillus enhanced TLR2 and TLR5 mRNA expression by nasal fibroblasts, TSLP protein and mRNA expression were inhibited only with siRNA against TLR2 but not with siRNA against TLR5. Fungi consist of several peptides, enzymes, and other antigenic components, which might be associated with the expression of TLR5. Although both Alternaria and Aspergillus enhanced TLRs mRNA expression, Aspergillus did not induced the production of TSLP. Considering these findings, we need to confirm which component of fungi is associated with the expression of TLR in nasal fibroblasts and the intracellular signal pathway which can induce the production of TSLP. Unlike nasal fibroblasts, synovial fibroblasts release TSLP in response to polyI:C (TLR3 lignad) and LPS (TLR4 lignad).18 Human fibroblasts are not homogenous populations and they express different structural and functional features that are dependent on their location within the body.14 This means fibroblasts from different anatomic sites and pathologic conditions determine characteristics and phenotypes of fibroblasts.

Our findings demonstrate unique characteristics of nasal fibroblasts in which fungi induced TSLP mRNA expression and TSLP protein production from primary nasal fibroblasts. TLR2 is thought to contribute to the production of TSLP. This TSLP can stimulate airway mucosal dendritic cells, which leads to the subsequent development of Th2 immune response in sinonasal mucosa. These immune responses may be involved in the initiation and amplification of CRS with nasal polyps

Environmental Immunology: Lessons Learned from Exposure to a Select Panel of Immunotoxicants.
Exposure to environmental contaminants can produce profound effects on the immune system. Many classes of xenobiotics can significantly suppress or enhance immune responsiveness depending on the levels (i.e., dose) and context (i.e., timing, route) of exposure. Although defining the effects that toxicants can have on the immune system is a valuable component to improving public health, environmental immunology has greatly enhanced our understanding of how the immune system functions and has provided innovative avenues to explore new immunotherapies. This Brief Review focuses on three examples of how immunotoxicology has benefitted the field of immunology, presenting information on the aryl hydrocarbon receptor signaling pathway, the immunomodulatory effects of nanomaterials, and the impact of xenobiotic exposure on the developing immune system. Collectively, contributions from immunotoxicology have significantly enhanced public health and spurred seminal advances in both basic and applied immunology.
https://www.ncbi.nlm.nih.gov/pubmed/27044635

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Co-morbid diseases were most strongly associated with CRS cases who reported smell loss and facial pain and/or pressure and had the weakest associations with CRS cases who did not report these symptoms.
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Real-life study showing uncontrolled rhinosinusitis after sinus surgery in a tertiary referral center.
https://www.ncbi.nlm.nih.gov/pubmed/27392210

Short-course oral steroids alone for chronic rhinosinusitis.
All of the adverse events results are based on low quality evidence.More research in this area, particularly research evaluating patients with chronic rhinosinusitis without nasal polyps, longer-term outcomes and adverse effects, is required.There is no evidence for oral steroids compared with other treatments
https://www.ncbi.nlm.nih.gov/pubmed/27113367
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please, washing the sinuses are the only option when you have severe chronic rhinosinusitis and severe reactivity to steroids, glad I didn't try surgery!!!!!!!!!!!!!!!
 

barbc56

Senior Member
Messages
3,657
please, washing the sinuses are the only option when you have severe chronic rhinosinusitis and severe reactivity to steroids, glad I didn't try surgery!!!!!!!!!!!!!!!

Are there other options treating chronic rhinosinusitis if you react to steroids?

I have a hard time taking steroids. I feel like I'm going to climb the walls and/or become irritable. Very irritable. I don't know if I'm remembering correctly but it seems my doctor said you can get around this reaction but maybe I dreamt that !:rolleyes:

I have heard you need to be careful using a netti pot, if this is the method you are talking about to clean out the sinuses, as it can spread infection from the nasal cavities, to other parts of the body. However, I also know numerous people who swear by it.

It does make sense that surgery would be a last resort but this information is way over my head.

I think I need to give your citations more than a cursory look.

Thanks for the info.
 
Last edited:

osisposis

Senior Member
Messages
389
depending on severeity surgery may not be what you want to do, I try to stay out of the "giving advice" tho. I don't use a neti pot. I use distilled water and sea salt, that's it. and blow blow blow after use. if you fell like your getting inflammation or infection afterwards might be good idea to wash again. I didn't fallow anyone advice I just did it when I felt the need, I also carried with me for a long time a bottle where apon known re-exposure to any of my triggers,ect. that caused the inflammation to start I'd use it again. basicly washing my sinuses when a re-exposure happens stops the progress of affects to the brain. it's been one of the few things I learned to do to help myself. and it didn't matter what was the trigger allergic or non-allergic. voc's,particles,allergens,irritants,gases,fumes,ect.