Increased Protein Citrullination as a Trigger for Resident Immune System Activation, Intraretinal Inflammation, and Promotion of Anti-retinal Autoimmunity: Intersecting Paths in Retinal Degenerations of Potential Therapeutic Relevance

Phosphocitrate (PC) inhibited calcium crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms remain elusive. This study sought to determine PC targeted genes and the expression of select PC targeted genes in OA menisci to test hypothesis that PC exerts its disease modifying activity in part by reversing abnormal expressions of genes involved in OA. We found that PC downregulated the expression of numerous genes classified in immune response, inflammatory response, and angiogenesis, including chemokine (C-C motif) ligand 5, Fc fragment of IgG, low affinity IIIb receptor (FCGR3B), and leukocyte immunoglobulin-like receptor, subfamily B member 3 (LILRB3). In contrast, PC upregulated the expression of many genes classified in skeletal development, including collagen type II alpha1, fibroblast growth factor receptor 3 (FGFR3), and SRY- (sex determining region Y-) box 9 (SOX-9). Immunohistochemical examinations revealed higher levels of FCGR3B and LILRB3 and lower level of SOX-9 in OA menisci. These findings indicate that OA is a disease associated with immune system activation and decreased expression of SOX-9 gene in OA menisci. PC exerts its disease modifying activity on OA, at least in part, by targeting immune system activation and the production of extracellular matrix and selecting chondroprotective proteins.

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A mechanistic study of immune system activation by fusion of antigens with the ligand-binding domain of CTLA4

Cancer Immunology Immunotherapy ◽

10.1007/s00262-006-0153-7 ◽

2006 ◽

Vol 55 (12) ◽

pp. 1504-1514 ◽

Cited By ~ 3

Author(s):

Dhanalakshmi Chinnasamy ◽

Matt Tector ◽

Nachimuthu Chinnasamy ◽

Kate Dennert ◽

Karen M. Kozinski ◽

...

Keyword(s):

Immune System ◽

Ligand Binding ◽

Binding Domain ◽

Ligand Binding Domain ◽

Mechanistic Study ◽

Immune System Activation ◽

System Activation

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Peer Review #2 of "Effects of invasion history on physiological responses to immune system activation in invasive Australian cane toads (v0.1)"

10.7287/peerj.3856v0.1/reviews/2 ◽

2017 ◽

Author(s):

G Vimercati

Keyword(s):

Immune System ◽

Peer Review ◽

Physiological Responses ◽

Invasion History ◽

Immune System Activation ◽

System Activation

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Deoxycorticosterone acetate-salt hypertension activates placental growth factor in the spleen to couple sympathetic drive and immune system activation

Cardiovascular Research ◽

10.1093/cvr/cvy001 ◽

2018 ◽

Vol 114 (3) ◽

pp. 456-467 ◽

Cited By ~ 13

Author(s):

Marialuisa Perrotta ◽

Andrea Lori ◽

Lorenzo Carnevale ◽

Stefania Fardella ◽

Giuseppe Cifelli ◽

...

Keyword(s):

Immune System ◽

Growth Factor ◽

Placental Growth Factor ◽

Deoxycorticosterone Acetate ◽

Immune System Activation ◽

Acetate Salt ◽

Salt Hypertension ◽

System Activation

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Abstract P145: Renal Inflammation and Injury is Associated with Increased Lymphangiogenesis in Hypertension

Hypertension ◽

10.1161/hyp.68.suppl_1.p145 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Sterling C Kneedler ◽

Lauren Phillips ◽

Kayla R Hudson ◽

Katharine M Beckman ◽

Alan R Parrish ◽

...

Keyword(s):

Blood Pressure ◽

Immune System ◽

Immune Cells ◽

Lymphatic Vessels ◽

Macrophage Infiltration ◽

Shr Rats ◽

Renal Inflammation ◽

Immune System Activation ◽

System Activation ◽

Fischer Rats

Hypertension is associated with immune system activation and inflammation. Renal infiltration of both innate and adaptive immune cells contributes to injury, dysfunction, and increased blood pressure. Activated immune cells that exit blood vessels into the interstitium then travel through lymphatic vessels to draining lymph nodes where they signal to other immune cells to increase the immune response. It is unknown how renal lymphatic vessels change in the context of hypertension, immune system activation, inflammation, and injury. We hypothesized that renal macrophage infiltration, inflammation, and injury would significantly increase lymphangiogenesis in various strains of rats. SHR rats that exhibit hypertension and renal injury (SHR-A3 strain) had significantly increased numbers of renal lymphatic vessels at 40 weeks of age compared to WKY controls (total of 3 fields of view: 52 ± 1 vs. 28 ± 1; p<0.05). This was associated with increased renal macrophage infiltration. SHR rats that exhibit hypertension but minimal renal injury (SHR-B2 strain) had significantly less renal lymphatic vessel numbers compared to WKY controls (25 ± 2 vs. 28 ± 1; p<0.05) and normal levels of macrophages. The signals for lymphangiogenesis, VEGF-C and its receptor VEGF-R3, were both increased significantly at the protein level in the kidneys of SHR-A3 rats at 18 weeks but not different in the kidneys of SHR-B2 rats compared to WKY controls. To test whether the increased lymphangiogensis is due to hypertension and/or renal inflammation and injury, we obtained kidneys from Fischer 344 rats that exhibit normal blood pressure but develop renal inflammation and injury as they age. Compared to kidneys from control 4-month old Fischer rats, kidneys from 20-month and 24-month old Fischer rats had significantly increased numbers of lymphatic vessels (32 ± 3 vs. 74 ± 1 vs. 110 ± 6, respectively; p<0.05) and this was also associated with increased macrophage infiltration. Protein levels of VEGF-C and VEGF-R3 were increased significantly in 20-month old Fischer rats compared to 4-month old controls. These data together demonstrate that renal immune cell infiltration, inflammation, and injury increases lymphangiogenesis.

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Immune System Activation in Perioperative Thrombectomy Patients: Preliminary Retrospective Study

World Neurosurgery ◽

10.1016/j.wneu.2019.05.044 ◽

2019 ◽

Vol 128 ◽

pp. e966-e969

Author(s):

Skylar Trott ◽

Olga Vsevolozhskaya ◽

Keith Pennypacker ◽

Abdulnasser Alhajeri ◽

Justin F. Fraser

Keyword(s):

Immune System ◽

Retrospective Study ◽

Immune System Activation ◽

System Activation

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The Complexity of the Innate Immune System Activation in Stroke Pathogenesis

Neuroinflammation ◽

10.1002/9781118732748.ch5 ◽

2015 ◽

pp. 71-85

Author(s):

María Isabel Cuartero ◽

Ignacio Lizasoain ◽

María Ángeles Moro ◽

Ivan Ballesteros

Keyword(s):

Immune System ◽

Innate Immune System ◽

Innate Immune ◽

Immune System Activation ◽

System Activation

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Uric acid and inflammation in kidney disease

AJP Renal Physiology ◽

10.1152/ajprenal.00272.2019 ◽

2020 ◽

Vol 318 (6) ◽

pp. F1327-F1340 ◽

Cited By ~ 2

Author(s):

Su Woong Jung ◽

Su-Mi Kim ◽

Yang Gyun Kim ◽

Sang-Ho Lee ◽

Ju-Young Moon

Keyword(s):

Uric Acid ◽

Immune System ◽

Kidney Disease ◽

Biological Effects ◽

Experimental Studies ◽

Epidemiologic Studies ◽

Causative Role ◽

Immune System Activation ◽

Progression Of Kidney Disease ◽

System Activation

Asymptomatic hyperuricemia is frequently observed in patients with kidney disease. Although a substantial number of epidemiologic studies have suggested that an elevated uric acid level plays a causative role in the development and progression of kidney disease, whether hyperuricemia is simply a result of decreased renal excretion of uric acid or is a contributor to kidney disease remains a matter of debate. Over the last two decades, multiple experimental studies have expanded the knowledge of the biological effects of uric acid beyond its role in gout. In particular, uric acid induces immune system activation and alters the characteristics of resident kidney cells, such as tubular epithelial cells, endothelial cells, and vascular smooth muscle cells, toward a proinflammatory and profibrotic state. These findings have led to an increased awareness of uric acid as a potential and modifiable risk factor in kidney disease. Here, we discuss the effects of uric acid on the immune system and subsequently review the effects of uric acid on the kidneys mainly in the context of inflammation.

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