From peripherally unsubstituted subphthalocyanines with anti-inflammatory activity on macrophages to tri-iodo derivatives with adjuvant and immunostimulatory functions

2019 ◽  
Vol 23 (01n02) ◽  
pp. 56-62 ◽  
Author(s):  
Furkan Ayaz ◽  
Abdulcelil Yuzer ◽  
Mine Ince

In this study we evaluated the impact of iodine substitution on the ability of subphthalocyanines (SubPc) to stimulate or regulate the function of macrophages. Previous studies have focused on the usage of phthalocyanines and their derivatives as treatment options against different types of cancer. In order to obtain better prognosis rates, their possible effects on the immune system cells should be delineated. Unique subphthalocyanines were designed and synthesized by our group and a derivative was generated via iodine substitution. In our study we further tested the effects of the new Subpcs on macrophage cell lines. Macrophages play an important role in the immune system through cytokine production and antigen presentation to other types of the immune system cells. They can define the type and the strength of the immune responses against a particular danger signal. Based on pro-inflammatory cytokine (TNF[Formula: see text], IL1[Formula: see text] and IL6) production levels by macrophages, unsubstituted SubPc had anti-inflammatory properties. However, iodine substitution on the same SubPc created a completely opposite effect since these iodo-substituted SubPc exerted an immunostimulatory effect on macrophages based on significant increases in the pro-inflammatory cytokine production levels compared to the untreated controls. While SubPcs can be used to suppress the pro-inflammatory activities of the macrophages, iodine-substituted SubPcs have potentials to be used as adjuvants and immunostimulatory molecules.

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 495-495
Author(s):  
Qiaozhi Zhang ◽  
Elvira Gonzalez de Mejia

Abstract Objectives To investigate the impact of cyanidin-3-O-glycoside (C3G) and its two major phenolic acid metabolites, protocatechuic acid (PCA) and ferulic acid (FA), on macrophage (MФ) factor-induced inflammation and mitochondrial dysfunction in 3T3-L1 adipocytes. Methods Secretory factors from lipopolysaccharide (LPS)-stimulated RAW 274.7 MФ were used to treat adipocytes to simulate the MФ-adipocyte crosstalk in adipose tissue. Alteration of inflammatory responses, including pro-/anti-inflammatory cytokine production and pro-inflammatory signaling pathway activation were evaluated. Mitochondrial respiration, biogenesis and function in MФ factor-induced adipocytes were investigated and the potential role of C3G, PCA and FA was compared. The AMPK-stimulating actions of PCA were explored via determining its impacts on the phosphorylation pattern of key proteins in the AMPK system. Results In LPS-conditioned media (CM)-treated adipocytes, C3G, PCA and FA suppressed pro-inflammatory cytokine production (TNF-α: −29.0 to −66.2%; IL-6: −6.6 to −38.2%) and enhanced anti-inflammatory cytokine secretion (adiponectin: 16.1–173.3%) in a dose-dependent manner (P < 0.05). C3G, PCA, and FA down-regulated the expression levels of phosphorylated IκBα and JNK in LPS-CM-stressed adipocytes by 50.5–54.5% and 40.3–56.7% (P < 0.05), respectively. C3G, PCA, and FA alleviated MФ factor-triggered oxidative stress via down-regulating mitochondrial superoxide and mitochondrial dysfunction by up-regulating mitochondrial respiration, in terms of adenosine triphosphate production, oxygen consumption and citrate synthase activity. Compared with C3G and FA, PCA showed better capacity in modulating inflammation and mitochondrial dysregulation in LPS-CM-treated adipocytes (P < 0.05). Further, treatment with PCA increased the AMPK, LKB1, CAMKII, p53, and Akt phosphorylation status while decreased activations in the ACC, mTOR, p70S6k and HSL. Conclusions Metabolites of C3G, primarily PCA, alleviated adipogenesis-induced inflammation and mitochondrial alteration in adipocytes, thus having potential implications to prevent adipogenesis-associated disorders. Funding Sources USDA-NIFA-HATCH 1,017,440.


Blood ◽  
2012 ◽  
Vol 119 (19) ◽  
pp. 4430-4440 ◽  
Author(s):  
Thomas Duhen ◽  
Rebekka Duhen ◽  
Antonio Lanzavecchia ◽  
Federica Sallusto ◽  
Daniel J. Campbell

Abstract FOXP3+ regulatory T (Treg) cells are a broadly acting and potent anti-inflammatory population of CD4+ T cells essential for maintaining immune homeostasis and preventing debilitating autoimmunity. Based on chemokine receptor expression, we identified distinct populations of Treg cells in human blood expected to colocalize with different Th cell subsets. Although each population was functionally suppressive, they displayed unique patterns of pro- and anti-inflammatory cytokine production, differentially expressed lineage-specifying transcription factors, and responded differently to antigens associated with Th1 and Th17 responses. These results highlight a previously unappreciated degree of phenotypic and functional diversity in human Treg cells that allows subsets with unique specificities and immunomodulatory functions to be targeted to defined immune environments during different types of inflammatory responses.


2014 ◽  
Vol 192 (11) ◽  
pp. 5373-5381 ◽  
Author(s):  
Rosa Lavieri ◽  
Patrizia Piccioli ◽  
Sonia Carta ◽  
Laura Delfino ◽  
Patrizia Castellani ◽  
...  

2015 ◽  
Vol 465 (2) ◽  
pp. 271-279 ◽  
Author(s):  
James Ozanne ◽  
Alan R. Prescott ◽  
Kristopher Clark

We have discovered that bosutinib and dasatinib, which are protein tyrosine kinase inhibitors used in the clinic to treat human cancer, induce anti-inflammatory but block pro-inflammatory cytokine production by inhibiting the serine/threonine kinases known as the salt-inducible kinases.


2003 ◽  
Vol 9 (5) ◽  
pp. S35
Author(s):  
Jason R. Becker ◽  
Mary E. Keebler ◽  
Patricia A. Uber ◽  
Myung H. Park ◽  
Robert L. Scott ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document