Consequences of the interaction between IL-17 cytokines and airway smooth muscle cells in the pathogenesis of airway remodeling in Asthma
Bibliographic record
Abstract
Asthma is one of the most common chronic diseases that are considered as an important cause of morbidity and mortality worldwide. The morbidity of asthma stems from several factors, including but not limited to, the structural changes that occur in the lung of asthmatics known as airway remodeling. Thickening of airway smooth muscle (ASM) mass area is a fundamental feature of airway remodelling in asthma, which has been long discovered. Although airway smooth muscle cells (ASMCs) have been and still are extensively investigated for their major role in the increase in ASM mass, the reason behind this increase and the mechanisms mediating it are yet to be elucidated. In recent years, the functions of ASMCs as a source of inflammatory mediators and their migration ability have become a prominent subject in the investigation of asthma. Believing that ASMCs are a key effector in the pathogenesis of airway remodeling, we aimed to examine the inflammatory mediators derived from ASMCs, after IL-17 stimulation, and the extent of their influence on ASMC migration. Indeed, we found that IL-17/ASMC-derived mediators enhance ASMC migration through production of growth-related oncogene chemokines (GROs; GRO-α, GRO-β and GRO-γ). In addition, we investigated the regulatory mechanisms, the receptors responsible and the signaling pathways activated during ASMC migration induced by GRO-α, GRO-β and GRO-γ. We reported that GRO-γ requires two receptors, CXCR1 and CXCR2, and two signaling pathways, p38 and ERK 1/2 MAPK, to induce ASMC migration. We also demonstrated that GRO-α acts as a negative regulator of ASMC migration, alone or in combination with GRO-β and/or GRO-γ, via the decoy receptor; Duffy antigen receptor for chemokines (DARC). Interestingly, we found that the presence of DARC leads GRO-α to inhibit ASMC migration through preferential activation of ERK 1/2 MAPK pathway and dampening the activation of p38 MAPK pathway, whereas its absence leads GRO-α to enhance ASMC migration through binding to CXCR2 and activation of p38 MAPK pathway.Collectively, our results demonstrate that the interaction between IL-17 cytokines and ASMCs is capable of enhancing ASMC migration in an autocrine fashion through GRO production and suggest that GROs may play a role in the pathogenesis of airway remodeling in asthma.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".