Inflammation seems to be a kind of well known body reaction to many agressions. How it happens has been debated for decades. Physicians have gone throught the simplification of this subject in order to facilitate therapy. Many drugs work there but how they do that in detail is still under clarification. We can’t admonish ourselves (of course) for not being clear in the process we are attacking to. However, some insight has been recently presented by very sharp experts. How does it start? What are the steps in the development of the inflammatory disease? What factors are involved?
Some chemical factors are released during a noxious exposure. The DNA has the genes with the information required to produce those substances. The DNA is compressed in the nuclei of cells. DNA is packed in a compressed structure called chromatin. Chromatin is not only composed by DNA but also by proteins called histones. Histones are basic (not acid) proteins that give the skeleton of the chromosome. Histones (H2A, H2B, H3 and H4) form an octomer (8 units bound) with 2 units of each type. Around this octomer are base pairs of DNA (146) and together (octomer of histones and base pairs) constitute nucleosomes. Nucleosomes one after other then form the chromatin in the nucleus of the cell.
When the chromatin is closely packed as described there’s no chance for new formation of messenger RNA (the messenger carrying the key composition of many proteins, including proinflammatory).
Some molecules generate the de-essembling of the chromatin. These molecules are large and called coactivator molecules. Coactivator molecules have intrinsic “histone acetyltransferase activity”. This means that coactivatro molecules have the property to acetylate histones. Whe histones are acetylated their charge turns into negative wich open the chromatin structure. The result is the opening of DNA showing the genes to RNA polymerase. The gene transcription starts and a resultant messenger RNA now have the information with inflammatory proteins to act and potentiate the inflammatory process.
The exposure of cells to some interleukins and other chemokines results in acetylation of the aminoacid lysine in H4 (one of the histones in the nucleosomes). This lead to increased expression of genes encoding inflammatory proteins in this process.
To enjoy more an explanation about these molecular process I would refer to a Review written by Peter J. Barnes with many thoughts and facts around this fsacinating world of inflammation now turning into a more understandable process. (British Journal of Pharmacology 2006. 148;245-254)
Inflammation seems to be a kind of well known body reaction to many agressions. How it happens has been debated for decades. Physicians have gone throught the simplification of this subject in order to facilitate therapy. Many drugs work there but how they do that in detail is still under clarification. We can’t admonish ourselves (of course) for not being clear in the process we are attacking to. However, some insight has been recently presented by very sharp experts. How does it start? What are the steps in the development of the inflammatory disease? What factors are involved?
Some chemical factors are released during a noxious exposure. The DNA has the genes with the information required to produce those substances. The DNA is compressed in the nuclei of cells. DNA is packed in a compressed structure called chromatin. Chromatin is not only composed by DNA but also by proteins called histones. Histones are basic (not acid) proteins that give the skeleton of the chromosome. Histones (H2A, H2B, H3 and H4) form an octomer (8 units bound) with 2 units of each type. Around this octomer are base pairs of DNA (146) and together (octomer of histones and base pairs) constitute nucleosomes. Nucleosomes one after other then form the chromatin in the nucleus of the cell.
When the chromatin is closely packed as described there’s no chance for new formation of messenger RNA (the messenger carrying the key composition of many proteins, including proinflammatory).
Some molecules generate the de-essembling of the chromatin. These molecules are large and called coactivator molecules. Coactivator molecules have intrinsic “histone acetyltransferase activity”. This means that coactivatro molecules have the property to acetylate histones. Whe histones are acetylated their charge turns into negative wich open the chromatin structure. The result is the opening of DNA showing the genes to RNA polymerase. The gene transcription starts and a resultant messenger RNA now have the information with inflammatory proteins to act and potentiate the inflammatory process.
The exposure of cells to some interleukins and other chemokines results in acetylation of the aminoacid lysine in H4 (one of the histones in the nucleosomes). This lead to increased expression of genes encoding inflammatory proteins in this process.
To enjoy more an explanation about these molecular process I would refer to a Review written by Peter J. Barnes with many thoughts and facts around this fsacinating world of inflammation now turning into a more understandable process. (British Journal of Pharmacology 2006. 148;245-254)