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1.
Int Immunopharmacol ; 121: 110450, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37343372

RESUMO

Macrophages are involved in the pathogenesis of allergic rhinitis (AR), but how these macrophages are polarized to M1 or M2 type is undetermined. Long non-coding RNA growth arrest specific transcript 5 (GAS5) is upregulated in exosomes isolated from nasal mucus of AR patients (AR-EXO) and aggravates nasal symptoms in AR mice. In the present study, we are aimed to elucidate the potential role of GAS5 in macrophage polarization during AR pathogenesis. An AR mice model was constructed. The potential function of GAS5 was evaluated by western blot, RNA immunoprecipitation (RIP), biotinylated RNA pull-down assay, co-immunoprecipitation (co-IP) assay, flow cytometry, enzyme-linked immunosorbent assay (ELISA) assay, and immunohistochemistry (IHC) staining. We found that GAS5 is upregulated in ovalbumin-treated human nasal epithelial cells RPMI 2650 (OVA-EXO) and nasal mucus of AR mice. OVA-EXO treatment or forced GAS5 expression promoted M1 macrophage polarization of peripheral blood monocytes (PB monocytes) and THP-1 macrophages in vitro. GAS5 overexpression aggravated the allergic nasal symptoms induced by OVA in AR mice and facilitated M1 macrophage polarization and allergic inflammation, while knockdown of GAS5 exhibited opposite effects in vivo. GAS5 activated NF-кB signaling via suppressing autophagy-dependent degradation of IKKα/ß in macrophages. Furthermore, GAS5 acted as a scaffold to strengthen the interaction between mTORC1 and ULK1, thus impaired ULK1/ATG13-mediated autophagy via increasing mTORC1 activity. Finally, restored autophagy by ATG13 overexpression suppressed the effect of GAS5 on M1 macrophage polarization. In conclusion, these results suggested that exosomal transfer of GAS5 promoted M1 macrophage polarization via restraining mTORC1/ULK1/ATG13-mediated autophagy and subsequently activating NF-кB signaling in allergic rhinitis.


Assuntos
RNA Longo não Codificante , Rinite Alérgica , Animais , Humanos , Camundongos , Autofagia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , NF-kappa B/metabolismo , Rinite Alérgica/metabolismo , RNA Longo não Codificante/genética
2.
Appl Opt ; 61(26): 7632-7643, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36256363

RESUMO

Predicting the photophoretic force exerted on an optical absorptive particle in a gaseous medium is a challenging problem because the problems of electromagnetic scattering, heat transfer, and gaseous molecule dynamics are involved and coupled with each other. Based on the calculation of the source function distribution inside a homogeneous sphere excited by a Bessel beam using the generalized Lorenz-Mie theory, analytical expressions of the asymmetry vector, which is the key quantity in the calculation of photophoretic force, are given using the adjoint boundary value method. Numerical simulations are performed to analyze the influences of polarization, the half-cone angle, and the beam order of the incident beam, particle size, and absorptivity of the particle on the asymmetry vector for both on-axis and off-axis illuminations. Longitudinal and transverse photophoretic forces on a homogeneous sphere are displayed for the slip-flow regime of gaseous media. The results offer important insights into the working mechanism underpinning the development of heat-mediated optical manipulation techniques and the measurement of the refractive index of particles.

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