Role Of NF-kappa B Signaling Pathway In The Granulomatous Mastitis

Objective:Granulomatous lobular mastitis is a chronic inflammatory disease mainly occurring in the lobules of the breast.Non-caseous necrotizing granuloma is the main pathological feature.Up to now,the exact etiology and pathogenesis of the disease are not clear,so its treatment methods are varied,and there is no unified evaluation index of curative effect.Histologically,granulomatous lobular mastitis(GLM)is characterized by lobular granuloma composed of macrophages,monocytes,neutrophils,lymphocytes and non-caseous necrotic lesions.As granuloma is induced by macrophage infiltration and proliferation,macrophage activation can be considered as the central pathogenesis of GLM.Macrophages release various factors,including interleukin-1 beta(IL-1 beta),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-alpha)and inducible nitric oxide synthase(iNOS).All these mediators exist in the pathogenesis of inflammatory diseases and are recognized as biomarkers for assessing the severity of inflammation.The nuclear factor-kappa B(NF-kappa B)pathway is considered as an upstream signal,which can regulate the transcription of these inflammatory factors.In this study,we investigated the expression of interleukin-1 beta(IL-1 beta),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-alpha)in granulomatous lobular mastitis(GLM)by case-control study,and analyzed the correlation between the above factors,NF-kappa B signaling pathway and the pathogenesis of granulomatous lobular mastitis(GLM).Methods:Specimens from the Department of Mammary Surgery,Ganmei Hospital Affiliated to Kunming Medical University from December 2017 to July 2018 were collected.The basic information of patients,the history of marriage,childbearing and breast-feeding,the past history of breast diseases and other patient information were collected,and detailed patient files were created.According to the difference of pathological diagnosis after operation,one experimental group(group A)and two control groups(group B and group C)were set up.In the experimental group,18 cases of breast tissue with granulomatous lobular mastitis confirmed by pathology after operation were highly suspected.In the control group,20 cases of breast fibroadenoma were confirmed by pathology after operation and 20 cases of normal breast tissue were confirmed by pathology.The levels of interleukin-1 beta(IL-1 beta),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-alpha)were measured by ELISA.The expression of nuclear factor-kappa B(NF-kappa B)was observed by immunohistochemical staining.The expression of NF-kappa B inhibitor protein I-kappa B in cytoplasm was detected by Western blot.Results:The expression of cytokines IL-1beta,IL-6,TNF-alpha,nuclear factor-kappa B in the experimental group(GLM)was significantly different from that in the other two groups(P<0.05),but there was no significant difference between the two groups(P>0.05);the level of inhibitory protein I-kappa B alpha in the experimental group(GLM)was significantly different from that in the other two groups(P>0.05).There was no significant difference between the two groups(P>0.05).Conclusion:1.Cytokines interleukin-1beta(IL-1beta),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-alpha)and NF-kappa B play an important role in the pathogenesis of GLM;2.The pathogenesis of GLM may be related to the activation of NF-kappa B signaling pathway and the regulation of the release of cytokines interleukin-1beta(IL-1beta),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-alpha).Radiation is closely related;3.There was no significant correlation between the pathogenesis of breast fibroadenoma and NF-kappa B signaling pathway and cytokines;4.Further research on the specific inflammatory activation pathway of NF-kappa B needs to be carried out,which will lay a foundation for finding precise targets for the prevention and treatment of GLM.