Loss of SENP3 Mediated the Formation of Nasal Polyps in Chronic
Sinusitis by Increasing Macrophage Alternative Activation
Abstract
Background and aim: Small ubiquitin–like modifier (SUMO)-specific
protease (SENP)3 is a protease molecule that responds to reactive oxygen
species (ROS) with high sensitivity. However, the role of ROS and SENP3
in the formation of nasal polyps (NPs) remains unclear. This study aimed
to explore how SENP3 influenced the outcome of chronic rhinosinusitis
(CRS) by altering macrophage function, that is, the formation of NPs.
Methods: The alternative activation of macrophage (M2) was detected with
CD68+CD206+ in humans and CD206+ in mice. The nasal mucosa of patients
with CRS was tested using flow cytometry (CD68, CD80, and CD206) and
triple-color immunofluorescence staining (CD68, CD206, and SENP3). The
bone marrow–derived macrophages from SENP3 knockout and control mice
were stimulated with interleukin (IL)-4 and IL-13 to analyze alternative
macrophage polarization in vitro. An animal model of allergic rhinitis
was constructed using SENP3 knockout mice. CD206 was detected by
immunofluorescence staining. The thickening of eosinophil-infiltrated
mucosa was detected by Luna staining. Results: The number of CD68+
CD206+ M2 increased in the nasal mucosa of patients with CRS with NP
(CRSwNP) compared with patients with CRS without NP (CRSsNP), but with
no significant difference between the groups. SENP3 knockout increased
the polarization of F4/80+CD206+M2. Meanwhile, the number of CD206+M2
significantly increased in the allergic rhinitis model constructed using
SENP3 knockout mice and controls, with a more obvious proliferation of
the nasal mucosa. Conclusion: The downregulation of the expression of
macrophage SENP3 in the nasal mucosa in chronic sinusitis promoted the
formation of NPs.