The effect of Conjugated Linoleic Acid and its 9:11 and 10:12 isomers on the inflammatory profiles on monocytic / macrophage and endothelial cell systems

This  study  investigated  the  role  of  the  dietary  lipid  Conjugated  Linoleic  Acid  (CLA)  as  a 50:50  mixture  of  9:11  CLA  and  10:12  CLA  and  these  two  isoforms  used  individually,  in regulating   the   carboxymethyllysine   (CML)   induced   inflammatory   response   in   human monocytic, macrophage and endothelial cells.  CML is a glycated amadori product that has a crucial  role  in  activating  the  inflammation  in  type  2  diabetes  (T2D).  All  three  forms  of  the lipid   at   non-toxic   levels   were   capable   of   significantly   reducing   the   release   of   two inflammatory  cytokines  (TNF-α  and  IL-6)  in  monocytes  and  macrophages  and  IL-6  in endothelial  cells.  In  contrast  the  non-conjugated  Linoleic  Acid  (LA)  did  not  significantly reduce  these  cytokines  in  any  of  the  cell  types  investigated.  All  isomerswere  capable  of activating  both  forms  of  the  nuclear  transcription  factors  Peroxisome  Proliferator  Activated Receptors (PPAR) α and  in  monocytes  and  macrophages.  CLA  induced  significantly  the activation  in  the  transcription  factor  important  in  regulating  the  inflammatory  response, nuclear  factor-kappa  B  (NF-B).  However,  in  cells  treated  with  CML,  CLA  significantly reduced the activation of NF-B as measured by DNA binding in cells pre-treated with CML-suggesting  an  ability  to  trensrepress  the  activity of  NF-B,  possibly  in  conjunction  with  the PPARs  and  supporting  an  anti-inflammatory  role  for  the  lipid  in  activated  cells.  All  three forms  of  the  lipid  were  significantly  able  to  regulate  expression  of  the  receptor  for  glycated proteins  (RAGE)  in  monocytes,  macrophages  and  endothelial  cells.  Gene  reporter  assays demonstrated   that   in   endothelial   cells,   that   CLA   was   capable   of   suppressing   the transcriptional  activity  of  promoters  which  contain promoters  for  NF-κB response elements, either  as  part  of  a  recombinant  construct  or  as  a  cloned  fragment  of  the  human  RAGE promoter. Hence, in conclusion it would appear that the CLAs investigated in this study could significantly  suppress  the  inflammation  in  diseases  such  as  T2D  through  their  ability  to suppress NF-B leading to down-regulation of RAGE expression. Furthermore, these events appear to be consistent for all three forms of CLA investigated and in all three cell types-all with a critical role in the development of atherosclerosis.