Molecular mechanisms of altered mucociliary clearance in patients with chronic rhinosinusitis with nasal polyps (CRSwNP)

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OBJECTIVE

To analyze literature data on molecular mechanisms of development of mucociliary clearance alterations in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).

MATERIAL AND METHODS

The analysis of documents published up to 10 of March 2023 yr. in PubMed (Medline), Google Scholar and RSCI databases was carried out. A search was done by «cilia», «mucociliary», «mucus», «nasal polyp», «nasal polyposis», «CRSwNP» keywords and their Russian equivalents.

RESULTS AND CONCLUSION

The analysis of the publications shows a significant mucociliary clearance disturbance in CRSwNS which is caused by ciliary apparatus dysfunction due to altered ciliogenesis, on the one hand, and by affected characteristics of nasal mucus mainly as a result of increased MUC5AC secretion. These changes develop due to excess production of anti-inflammatory cytokines specific for CRSwNP, primarily IL-13, whose role in ciliary dysfunction is the most studied. A number of other cytokines, including IL-5, IL-6, tumor necrosis factor-α and interferon-γ also have a significant modulating effect on mucociliary transport in CRSwNP. The immediate molecular mechanisms mediating the influence of these cytokines on epithelial cells differentiation, ciliary activity or mucus secretion, may include activation of HIF-1, PI3K, TMEM16, NF-κB, STAT3/6, ERK signaling pathways, as well as modulation of transcription factors’ expression involved in ciliogenesis regulation. It is suggested that the impact of mucociliary clearance alterations on molecular mechanisms in patients with CRSwNP may increase efficacy of both therapeutic and surgical treatment methods.

Keywords:

chronic rhinosinusitis

nasal polyps

mucin

ciliogenesis

cytokines

Authors:

Alekseenko S.

Saint Petersburg Research Institute of Ear, Throat, Nose and Speech Ministry of Healthcare of Russia;
Mechnikov Northwest State Medical University Ministry of Healthcare of the Russia

ORCID: 0000-0002-3377-8711

Dvoryanchikov V.V.

Saint Petersburg ENT and Speech Research Institute

ORCID: 0000-0002-0925-7596

Artyushkin S.A.

Saint Petersburg Research Institute of Ear, Throat, Nose and Speech Ministry of Healthcare of Russia;
Mechnikov Northwest State Medical University Ministry of Healthcare of the Russia

ORCID: 0000-0003-4482-6157

Riazantsev S.V.

Saint Petersburg Research Institute of Ear, Throat, Nose and Speech Ministry of Healthcare of Russia

ORCID: 0000-0003-1710-3092

Skalny A.V.

RUDN University;
I.M. Sechenov First Moscow State Medical University (Sechenov University)

ORCID: 0000-0001-7838-1366

Barashkova S.V.

Saint Petersburg Research Institute of Ear, Throat, Nose and Speech Ministry of Healthcare of Russia

ORCID: 0000-0002-5618-4510

Krivopalov A.A.

St. Petersburg Research Institute of Ear, Throat, Nose and Speech

ORCID: 0000-0002-6047-4924

Turieva V.V.

Saint Petersburg Research Institute of Ear, Throat, Nose and Speech Ministry of Healthcare of Russia

ORCID: 0000-0002-1221-7210

Tinkov A.A.

RUDN University;
Institute for Cellular and Intracellular Symbiosis of the Ural Branch of the Russian Academy of Sciences

ORCID: 0000-0003-0348-6192

Received:

02.04.2023

Accepted:

15.09.2023

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