Chemokines constitute a family of chemoattractant cytokines and are subdivided into four families on the basis of the number and spacing of the conserved cysteine residues in the N-terminus of the protein. Chemokines play a major role in selectively recruiting monocytes, neutrophils, and lymphocytes, as well as in inducing chemotaxis through the activation of G-protein-coupled receptors. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. Both CCL2 and its receptor CCR2 have been demonstrated to be induced and involved in various diseases. Migration of monocytes from the blood stream across the vascular endothelium is required for routine immunological surveillance of tissues, as well as in response to inflammation. This review will discuss these biological processes and the structure and function of CCL2.

Monocyte chemoattractant protein-1 (MCP-1): an overview.

I. Introduction II. Molecular Aspects A. PPAR isotypes: identity, genomic organization and chromosomal localization B. DNA binding properties C. PPAR ligand-binding properties D. Alternative pathways for PPAR activation E. PPAR-mediated transactivation properties III. Physiological Aspects A. Differential expression of PPAR mRNAs B. PPAR target genes and functions in fatty acid metabolism C. PPARs and control of inflammatory responses D. PPARs and atherosclerosis E. PPARs and the development of the fetal epidermal permeability barrier F. PPARs, carcinogenesis, and control of the cell cycle IV. Conclusions

Peroxisome proliferator-activated receptors: nuclear control of metabolism.

Over the past few decades, researchers have established artificial enzymes as highly stable and low-cost alternatives to natural enzymes in a wide range of applications. A variety of materials including cyclodextrins, metal complexes, porphyrins, polymers, dendrimers and biomolecules have been extensively explored to mimic the structures and functions of naturally occurring enzymes. Recently, some nanomaterials have been found to exhibit unexpected enzyme-like activities, and great advances have been made in this area due to the tremendous progress in nano-research and the unique characteristics of nanomaterials. To highlight the progress in the field of nanomaterial-based artificial enzymes (nanozymes), this review discusses various nanomaterials that have been explored to mimic different kinds of enzymes. We cover their kinetics, mechanisms and applications in numerous fields, from biosensing and immunoassays, to stem cell growth and pollutant removal. We also summarize several approaches to tune the activities of nanozymes. Finally, we make comparisons between nanozymes and other catalytic materials (other artificial enzymes, natural enzymes, organic catalysts and nanomaterial-based catalysts) and address the current challenges and future directions (302 references).

Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes

Widmann, Christian, Spencer Gibson, Matthew B. Jarpe, and Gary L. Johnson. Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human. Physiol. Rev. 79: 143–180, 19...

Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human

Publisher Summary This chapter focuses on interleukin-8 (IL-8) and related chemotactic cytokines—namely, CXC and CC chemokines. IL-8 is the best known member of a new class of cytokines that are widely studied because of their ability to attract and activate leukocytes, and their potential role as mediators of inflammation. IL-8 was originally isolated from the culture supernatants of stimulated human blood monocytes and was identified as a protein of 72 amino acids with a molecular weight of 8383. The three-dimensional structure of IL-8 has been studied by nuclear magnetic resonance spectroscopy and X-ray crystallography. In concentrated solution, and on crystallization, IL-8 is present as a dimer. The first CC chemokine was identified after cloning by differential hybridization from human tonsillar lymphocytes and was termed LD78. The CC and CXC chemokines are similar in size and have an overall structure that is characterized by the two intrachain disulfide bonds, short N-terminal and long C-terminal sequences. It discusses the role of chemokines in pathology with skin inflammation because psoriasis was the first disease to be linked to overproduction of IL-8. Several independent studies document the occurrence of high levels of IL-8 in the synovial fluid of inflamed joints of patients with different forms of rheumatic diseases, osteoarthritis, and gout.

Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines.

Cutin, a biopolyester composed of hydroxy and epoxy fatty acids, is the barrier between the aerial parts of higher plants and their environment. Suberin a polymer containing aromatics and polyesters, functions as a barrier in underground parts, wound surfaces, and a variety of internal organs. The composition and probable structure of these polymers are discussed. The biosynthesis of the hydroxy, epoxy, and dicarboxylic acids of the polyesters from the common cellular fatty acids is elucidated. An extracellular enzyme transfers the hydroxy and epoxyacyl moieties from their coenzyme A derivatives to the growing polyester. The enzymes acting in the biodegradation of the polyesters have been isolated from fungi, pollen, and mammals and characterized. The function and possible practical implications of these polyester barriers are briefly discussed.

https://science.sciencemag.org/content/sci/208/4447/990.full.pdf

Biopolyester Membranes of Plants: Cutin and Suberin

Chemistry and biochemistry of natural waxes

Two billion people are latently infected with Mycobacterium tuberculosis (Mtb). Mtb-infected macrophages are likely to be sequestered inside the hypoxic environments of the granuloma and differentiate into lipid-loaded macrophages that contain triacylglycerol (TAG)-filled lipid droplets which may provide a fatty acid-rich host environment for Mtb. We report here that human peripheral blood monocyte-derived macrophages and THP-1 derived macrophages incubated under hypoxia accumulate Oil Red O-staining lipid droplets containing TAG. Inside such hypoxic, lipid-loaded macrophages, nearly half the Mtb population developed phenotypic tolerance to isoniazid, lost acid-fast staining and accumulated intracellular lipid droplets. Dual-isotope labeling of macrophage TAG revealed that Mtb inside the lipid-loaded macrophages imports fatty acids derived from host TAG and incorporates them intact into Mtb TAG. The fatty acid composition of host and Mtb TAG were nearly identical suggesting that Mtb utilizes host TAG to accumulate intracellular TAG. Utilization of host TAG by Mtb for lipid droplet synthesis was confirmed when fluorescent fatty acid-labeled host TAG was utilized to accumulate fluorescent lipid droplets inside the pathogen. Deletion of the Mtb triacylglycerol synthase 1 (tgs1) gene resulted in a drastic decrease but not a complete loss in both radiolabeled and fluorescent TAG accumulation by Mtb suggesting that the TAG that accumulates within Mtb is generated mainly by the incorporation of fatty acids released from host TAG. We show direct evidence for the utilization of the fatty acids from host TAG for lipid metabolism inside Mtb. Taqman real-time PCR measurements revealed that the mycobacterial genes dosR, hspX, icl1, tgs1 and lipY were up-regulated in Mtb within hypoxic lipid loaded macrophages along with other Mtb genes known to be associated with dormancy and lipid metabolism.

/pdf/mycobacterium-tuberculosis-uses-host-triacylglycerol-to-14f2t377gk.pdf

Mycobacterium tuberculosis Uses Host Triacylglycerol to Accumulate Lipid Droplets and Acquires a Dormancy-Like Phenotype in Lipid-Loaded Macrophages

Structure, Biosynthesis, and Biodegradation of Cutin and Suberin

Objective: Cerium oxide (CeO2) nanoparticles have been shown to protect cells in culture from lethal stress, but no protection in vivo has been reported. Cardiac-specific expression of monocyte chemoattractant protein (MCP)-1 in mice causes ischemic cardiomyopathy associated with activation of endoplasmic reticulum (ER) stress. The aim of this study was to assess the effects of CeO2 nanoparticles on cardiac function and remodeling as well as ER stress response in this murine model of cardiomyopathy.

Methods: MCP-1 transgenic mice (MCP mice) and wild-type controls were administered intravenously 15 nmol of CeO2 nanoparticles or vehicle only twice a week for 2 weeks. Cardiac function, myocardial histology, nitrotyrosine formation, expression of cytokines, and ER stress-associated genes were evaluated.

Results: Treatment with CeO2 nanoparticles markedly inhibited progressive left ventricular dysfunction and dilatation in MCP mice and caused a significant decrease in serum levels of MCP-1, C-reactive protein, and total nitrated proteins. The infiltration of monocytes/macrophages, accumulation of 3-nitrotyrosine, apoptotic cell death, and expression of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the myocardium were markedly inhibited by CeO2 nanoparticles. Expression of the key ER stress-associated genes, including glucose-regulated protein 78 (Grp78), protein disulfide isomerase (PDI), and heat shock proteins (HSP25, HSP40, HSP70), were also suppressed by CeO2 nanoparticles.

Conclusions: CeO2 nanoparticles protect against the progression of cardiac dysfunction and remodeling by attenuation of myocardial oxidative stress, ER stress, and inflammatory processes probably through their autoregenerative antioxidant properties.

Pappachan E. Kolattukudy

Papers

Biopolyester Membranes of Plants: Cutin and Suberin

Chemistry and biochemistry of natural waxes

Mycobacterium tuberculosis Uses Host Triacylglycerol to Accumulate Lipid Droplets and Acquires a Dormancy-Like Phenotype in Lipid-Loaded Macrophages

Structure, Biosynthesis, and Biodegradation of Cutin and Suberin

Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy.