The Role of the Complement System Classical and Alternative Pathways in the Pathogenesis of Lacrimal Gland Benign Lymphoepithelial Lesions

2021 ◽  
Author(s):  
Rui Liu ◽  
Jing Li ◽  
Mei Sun ◽  
Jinjin Wang ◽  
Nan Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Lacrimal Gland ◽  
Complement System ◽  
Immunohistochemical Staining ◽  
Rt Pcr ◽  
Alternative Pathways ◽  
Medical University ◽  
The Complement System ◽  
Lymphoepithelial Lesions

Abstract Objective: The complement system plays an important role in chronic inflammation and autoimmune diseases. On the basis of previous studies, this paper further analyzed the role of the complement system classical pathway and alternative pathway in the pathogenesis of lacrimal gland benign lymphoepithelial lesions (LGBLEL).Methods: Six cases of LGBLEL and six cases of orbital cavernous hemangioma (CH), diagnosed by histopathology in Beijing Tongren Hospital, Capital Medical University, between July 2010 and October 2013 were randomly selected for proteomic analysis. Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the signaling pathways of differentially expressed genes and proteins. Four LGBLEL and three orbital CH cases, diagnosed by histopathology in Beijing Tongren Hospital, Capital Medical University, between October 2018 and August 2019, were randomly selected as the experimental group and the control group, respectively. RT-PCR, immunohistochemical staining and western blotting were used to verify the genes and proteins related to the complement system signaling pathway.Results: The expression of complement system signaling pathway in LGBLEL tissue was significantly different (P<0.0001) compared with orbital CH, and C3, C5 and C9 were differentially expressed genes. RT-PCR results showed that mRNA expression levels of C1qA, C3, C5 and C9 related to the complement signaling pathway were higher in LGBLEL tissues than in orbital CH (P<0.0001). Immunohistochemical staining results showed that C1qA, C3, C5 and C9 protein expression was significantly higher in LGBLEL tissues than in orbital CH. Western blotting showed that the levels of C1qA, C3, C5 and C9 proteins were significantly higher in LGBLEL tissues than in orbital CH (P=0.0008; P=0.0375; P=0.0306; P=0.0073, respectively).Conclusion: Both the classical and alternative pathways of complement system are involved in the pathogenesis of LGBLEL.

scholarly journals The FcεRI signaling pathway is involved in the pathogenesis of lacrimal gland benign lymphoepithelial lesions as shown by transcriptomic analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jing Li ◽  
Rui Liu ◽  
Mei Sun ◽  
Jinjin Wang ◽  
Nan Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Lacrimal Gland ◽  
Immunohistochemical Staining ◽  
Transcriptomic Analysis ◽  
Control Groups ◽  
Benign Lymphoepithelial Lesion ◽  
Medical University ◽  
And Control ◽  
Lymphoepithelial Lesions

AbstractThis study aimed to analyze the role of the FcepsilonRI (FcεRI) signaling pathway in the pathogenesis of benign lymphoepithelial lesion of lacrimal gland (LGBLEL). Transcriptomic analysis was performed on LGBLEL and orbital cavernous hemangioma (CH) patients diagnosed via histopathology in Beijing Tongren Hospital, Capital Medical University, between July 2010 and October 2013. Four LGBLEL and three orbital CH patients, diagnosed between October 2018 and August 2019, were randomly selected as experimental and control groups, respectively. RT-PCR, immunohistochemical staining, and western blotting were used to verify genes and proteins related to the FcεRI signaling pathway. Transcriptomic analysis showed that the FcεRI signaling pathway was upregulated in the LGBLEL compared with the CH group. The mRNA expression levels of important genes including SYK, p38, JNK, PI3K, and ERK were significantly increased in the LGBLEL group (P = 0.0066, P = 0.0002, P = 0.0003, P < 0.0001, P < 0.0001, respectively). Immunohistochemical staining results showed that SYK, p38, and ERK were positively expressed in LGBLEL, while JNK and PI3K were not. The protein contents of P-SYK, P-p38, P-JNK, P-PI3K, and P-ERK were significantly higher in the LGBLEL than in the CH group (P = 0.0169, P = 0.0074, P = 0.0046, P = 0.0157, P = 0.0156, respectively). The FcεRI signaling pathway participates in the pathogenesis of LGBLEL.

The Involvement of the Fcεri Signaling Pathway in the Pathogenesis of Lacrimal Gland Benign Lymphoepithelial Lesions

2021 ◽  
Author(s):  
Jing Li ◽  
Rui Liu ◽  
Mei Sun ◽  
Jinjin Wang ◽  
Nan Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Western Blotting ◽  
Lacrimal Gland ◽  
Immunohistochemical Staining ◽  
Proteome Analysis ◽  
Control Group ◽  
Rt Pcr ◽  
Expression Levels ◽  
Benign Lymphoepithelial Lesion ◽  
Medical University

Abstract Objective: Benign lymphoepithelial lesion of lacrimal gland (LGBLEL) is a common orbital inflammatory disease with unknown pathogenesis. T his paper analyzed the role of the FcepsilonRI (FcεRI) signaling pathway in the pathogenesis of LGBLEL.Methods: Transcriptome sequencing and proteome sequencing were performed on LGBLEL and orbital CH diag nosed by histopathology in Beijing Tongren Hospital, Capital Medical University, between July 2010 and October 2013. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to jointly analyze the differentially expressed ge nes and proteins related to FcεRI signaling pathway. Four LGBLEL and three orbital CH diagnosed by histopathology in Beijing Tongren Hospital, Capital Medical University, between October 2018 and August 2019 were randomly selected as the experimental group and the control group, respectively. RT PCR, immunohistochemical staining, and western blotting were used to verify the genes and proteins related to the FcεRI signaling pathway.Results: Combined transcriptome and proteome analysis showed that the FcεRI signaling pathway was up regulated in LGBLEL (P=0.0040), and that the important proteins such as SYK, p38, JNK, PI3K, and ERK were highly expressed in LGBLEL tissues. RT PCR results showed that the mRNA expression levels of SYK, p38, JNK, PI3K, and ERK wer e significantly increased in the LGBLEL group (P=0.0066, P=0.0002, P=0.0003, P<0.0001, P<0.0001, respectively). Immunohistochemical staining results showed that the protein expression levels of SYK, p38, JNK, PI3K, and ERK in LGBLEL tissues were significan tly higher than in orbital CH. Western Blotting showed that the protein contents of p SYK, p p38, p JNK, p PI3K, and p ERK were significantly higher than in orbital CH (P=0.0169, P=0.0074, P=0.0046, P=0.0157, P=0.0156, respectively). Conclusion: The genes and proteins related to the FcεRI signaling pathway are up regulated in LGBLEL, indicating that the FcεRI signaling pathway participates in the pathogenesis of LGBLEL.

scholarly journals IMMU-35. COMPLEMENT SYSTEM AND GLIOBLASTOMA: AN INTRICATE RELATIONSHIP

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi126-vi126
Author(s):  
Sandeep Mittal ◽  
Shayak Sengupta ◽  
Sabbir Khan ◽  
Kain McGee ◽  
Kristin Alfaro-Munoz ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Complement System ◽  
Complement Activation ◽  
Receptor Expression ◽  
High Expression ◽  
Rt Pcr ◽  
Expression Levels ◽  
Human Gbm ◽  
The Complement System

Abstract The complement system is a vital part of the innate immune system which plays a critical role in immune surveillance and inflammatory processes. Malignant and host cells express various complement inhibitory proteins on their surface to protect against complement mediated cytotoxicity. Imbalanced complement activation triggers inflammation and alters the tumor microenvironment. Complement activation has been shown to induce proliferation and migration of breast, ovarian and lung cancer cells. At this time, the expression and functional role of the complement cascade in glioblastoma (GBM) remain elusive. Here, we investigated the role of complement proteins and their receptor expression in human primary glioma stem-like cells (GSCs) and human GBM tissues. Western blot data demonstrated a high level of expression of central complement components and their receptors in GSCs. RT-PCR data further confirmed the high expression of complement genes which was similar or higher to normal human astrocytes (HA), a cell with high baseline expression levels of complement genes. Flow cytometry analysis revealed that almost 95% of GSCs expressed the anaphylatoxin complement receptors C3aR and C5aR on their cell surfaces which was consistent with our immunohistochemistry analysis of freshly resected GBM tissues. Furthermore, anaphylatoxin C5a exposure increased the proliferation of a subgroup of GSCs while reduced in another subset. Interestingly, C5a exposure was found to increase the expression of various pro-inflammatory markers in GSCs with reduced proliferation. Fluorescence-activated cell sorting (FACS) analysis of freshly isolated human GBM tissue revealed predominant expression of C5aR on cancer cells (CD11b-/CD45- cells) rather than on immune cells. RT-PCR analysis also demonstrated high expression levels of complement genes with concomitant decrease in complement inhibitory genes in human GBM tissue. Evaluation of the differential role of the complement system in GSCs along with their role in in vivo glioma models is ongoing.

scholarly journals Special Issue: The Role of Complement in Cancer Immunotherapy

Antibodies ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 29
Author(s):  
Ronald P. Taylor
Keyword(s):  
Cancer Immunotherapy ◽  
Complement System ◽  
Immune Defense ◽  
Special Issue ◽  
The Complement System ◽  
Critical Aspects

The complement system plays an important role in critical aspects of immune defense and in the maintenance of homeostasis in the bloodstream, as well as in essentially all tissues and organs [...]

The role of the complement system in hereditary angioedema

2017 ◽  
Vol 89 ◽  
pp. 59-68 ◽  
Author(s):  
Dorottya Csuka ◽  
Nóra Veszeli ◽  
Lilian Varga ◽  
Zoltán Prohászka ◽  
Henriette Farkas
Keyword(s):  
Complement System ◽  
Hereditary Angioedema ◽  
The Complement System

The role of paramyosin from blood fluke Schistosoma mansoni in inhibition of the complement system

2008 ◽  
Vol 45 (16) ◽  
pp. 4172
Author(s):  
Lina Grekin ◽  
Ram Cohen ◽  
James M. Sodetz ◽  
Daniel Gold ◽  
Zvi Fishelson
Keyword(s):  
Schistosoma Mansoni ◽  
Complement System ◽  
Blood Fluke ◽  
The Complement System

scholarly journals Activation of the complement system by pathogenic fungi.

1996 ◽  
Vol 9 (1) ◽  
pp. 34-46 ◽  
Author(s):  
T R Kozel
Keyword(s):  
Complement System ◽  
Host Resistance ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Complement Cascade ◽  
Experimental Animals ◽  
Molecular Bases ◽  
The Complement System

Fungi have been studied as prototype activators of the complement cascade since the early 1900s. More recently, attention has focused on the role of the complement system in the pathogenesis of fungal infections. The interactions of Cryptococcus neoformans and Candida albicans with the complement system are the most widely characterized; however, all pathogenic fungi examined to date have the ability to initiate the complement cascade. The molecular mechanisms for initiation and regulation of the complement cascade differ from one fungus to another, most likely reflecting differences in the structure of the outer layers of the cell wall. The molecular bases for such differences remain to be identified. Studies of mycoses in experimental animals with induced or congenital deficiencies in the complement system demonstrate that complement is an important innate system for control of fungal infection. Contributions to host resistance include opsonization and generation of inflammatory mediators. Inflammation induced by chemotactic products of the complement system may contribute to the pathogenesis of some fungal infections.

scholarly journals The role of the lectin pathway of the complement system in SARS-CoV-2 lung injury

2020 ◽  
Author(s):  
Mineia Alessandra Scaranello Malaquias ◽  
Ana Carolina Gadotti ◽  
Jarbas da Silva Motta-Junior ◽  
Ana Paula Camargo Martins ◽  
Marina Luise Viola Azevedo ◽  
...  
Keyword(s):  
Lung Injury ◽  
Complement System ◽  
Lectin Pathway ◽  
The Complement System
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