Chapter 5 Proinflammatory cytokines in CRP baseline regulation
Section snippets
C‐Reactive Protein and Inflammation
CRP is classified as one of the classical acute‐phase proteins by its biological properties. It is synthesized and secreted to the blood by the liver after initiating signals from the body, for example, infection, trauma, or tissue damage, mediated by inflammatory cytokines. By structure, CRP belongs to pentraxin protein family and is part of the soluble innate immune system where it plays an important role as a pattern‐recognition molecule [1]. After binding a ligand, for example,
Demographic, Metabolic, and Socioeconomic Factors
Population studies have shown that serum CRP concentrations are broadly distributed and highly skewed to the right in apparently healthy people [[32], [58]], that is, most individuals are grouped together in the lowest values measured, the rest being dispersed up to 10 mg/l or more. CRP concentrations have been found to increase slightly with age and to differ between males and females [[59], [60]], females tending to have slightly increased concentrations compared to males [[61], [62]].
Proinflammatory Cytokines
The main proinflammatory cytokine inducers of CRP in hepatic cells are the interleukins‐1 (IL‐1) and ‐6 (IL‐6) and recently found IL‐17. Generally, cytokines transduce signals from outside the cell into the cells via specific receptors. Compared to hormone or growth or factor receptors, the number of cytokine receptors on cell surfaces is usually a hundred time less than that of hormone or growth factor receptors [103]. Inside the cells, a given set of kinases, phosphatases and transcription
Signaling Through IL Receptors
Signaling from the IL receptors to CRP induction is done through several signaling molecules and transcription factors. The regulation of CRP expression is done at transcriptional level and focuses on the 300‐bp long CRP promoter. Most of the CRP expression studies have been done in Hep3B cells, and these are described below.
The promoter region of CRP of Hep3B cells harbors binding sites for transcription factors HNF‐1α (hepatic nuclear factor 1α), OCT‐1 (octamer-binding transcription factor
Genetic Polymorphisms
Serum CRP concentrations are influenced by genetic polymorphisms of various genes. Polymorphisms of several proinflammatory cytokine genes have been reported to associate with CRP concentration. A summary of these studies is presented in Table 1. Majority of the studies are quite small, and adjustment for covariates is lacking in many papers. Besides cytokine genes, polymorphisms in other genes also show association with CRP concentrations, including CRP, LEPR, HNF1A, APOE, GCKR, IRAK1, FTO [
Conclusions
Low grade inflammation is being accepted to lie behind many common diseases. However, it should be kept in mind that minor elevation in one of the major inflammatory markers measured in clinical practice today, CRP, can be the result of physiological homeostasis maintenance caused by minor tissue damage in our everyday life, reflecting CRP's role as a waste management molecule helping phagocytes remove cellular debris. Infection or a full blown inflammation with classical symptoms of redness,
Acknowledgment
I would like to thank Prof. M Hurme for valuable discussions during the manuscript preparation.
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