Synergistic interaction between C5a and NOD2 signaling in the regulation of chemokine expression in RAW 264.7 macrophages

The innate immune response is a complex process involving multiple pathogen-recognition receptors, including toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors. Complement is also a critical component of innate immunity. While complement is known to interact with TLR-mediated signals, the interactions between NOD-like receptors and complement are not well understood. Here we report a synergistic interaction between C5a and Nod2 signaling in RAW 264.7 marophages. Long-term treatment with muramyl dipeptide (MDP), a NOD2 ligand, enhanced C5a-mediated expression of chemokine mRNAs in RAW 264.7 cells. This response was dependent on NOD2 expression and was associated with a decrease in expression of C5L2, a receptor for C5a which acts as a negative modulator of C5a receptor (C5aR) activity. MDP amplified C5a-mediated phosphorylation of p38 MAPK. Treatment of RAW264.7 cells with an inhibitor of p38 attenuated the synergistic effects of C5aon MDP-primed cells on MIP-2, but not MCP-1, mRNA. In contrast, inhibition of AKT prevented C5a stimulation of MCP-1, but not MIP-2, mRNA, in MDP-primed cells. Taken together, these data demonstrated a synergistic interaction between C5a and NOD2 in the regulation of chemokine expression in macrophages, associated with a down-regulation of C5L2, a negative regulator of C5a receptor activity.

Conservation Status and Therapeutic Potential of <i>Saussurea lappa</i>: An Overview

Plants from the start are being used for the welfare of human and animals. About 25,000 biological active compounds are reported by different scientists. Plants itself are a complete treatment bioagent. People are still using plants and their decoction for different diseases. Saussurea lappa Clarke is the member of family Compositae. This plant is famous due to its high medical importance. The plant is commonly named as Kuth root or costus and has wide use for anticancer, antiulcer, hepatoprotective, anti-viral, anticonvulsant, antiarthritic, activities. Biologically active substance of in this plant is lactone cynaropicrin, dehydrocostus, germacrene,?lappadilactone. This plant can be used to extract such bioactive compounds which can help the scientist to discover new and potential drugs. Due to such chemical composition and medicinal importance this review has been prepared for the awareness of the people to conserve their medicinal plants which can be used for potential drug discovery.

FLK is an mRNA m^(6)A reader that regulates floral transition by modulating the stability and splicing of FLC in Arabidopsis

N^(6)-methyladenosine(m^(6)A),which is added,removed,and interpreted by m^(6)A writers,erasers,and readers,respectively,is the most abundant modification in eukaryotic mRNAs.The m^(6)A marks play a pivotal role in the regulation of floral transition in plants.FLOWERING LOCUS K(FLK),an RNA-binding protein harboring K-homology(KH)motifs,is known to regulate floral transition by repressing the levels of a key floral repressor FLOWERING LOCUS C(FLC)in Arabidopsis.However,the molecular mechanism underlying FLK-mediated FLC regulation remains unclear.In this study,we identified FLK as a novel mRNA m^(6)A reader protein that directly binds the m^(6)A site in the 3ʹ-untranslated region of FLC transcripts to repressing FLC levels by reducing its stability and splicing.Importantly,FLK binding of FLC transcripts was abolished in vir-1,an m^(6)A writer mutant,and the late-flowering phenotype of the flk mutant could not be rescued by genetic complementation using the mutant FLKm gene,in which the m^(6)A reader encoding function was eliminated,indicating that FLK binds and regulates FLC expression in an m^(6)A-dependent manner.Collectively,our study has addressed a long-standing question of how FLK regulates FLC transcript levels and established a molecular link between the FLK-mediated recognition of m^(6)A modifications on FLC transcripts and floral transition in Arabidopsis.