Constitutive and inflammatory induction of alpha and beta chemokines in human first trimester forebrain astrocytes and neurons.
Chemokine effects on leukocyte infiltration into the central nervous system (CNS) are key events in the inflammatory processes of neuroimmunologic and neuroinfectious diseases. Because, chemokines may play important roles in proliferation and differentiation of brain cells and in the initiation and progression of CNS inflammatory disorders, we analyzed constitutive and inflammatory-induced expression of alpha and beta chemokines in human first trimester forebrain cells. Constitutive induction of IL-8, MIP-1alpha, MIP-1beta, MCP-1 and regulated on activation, normal T-cell expressed, and secreted (Rantes) was detected in cryostat sections of embryonic forebrains in an age-dependent manner. Dissociated cell cultures were studied for spontaneous chemokine induction and after stimulation with the trypanosome lymphocyte triggering factor (TLTF), a novel trypanokine secreted by African trypanosomes that triggers a complex of immune responses. LPS and variant surface glycoprotein (VSG) were used as controls. In cultures, unstimulated cells expressed minimal chemokine levels except for Rantes. In response to TLTF and LPS, but not VSG, all chemokines were highly induced at the mRNA and protein levels in a dose- and age-dependent manner. Combined assays (in situ hybridization and immunohistochemistry) revealed that astrocytes and neurons are major sources for chemokines. These results illustrate the ability of resident brain cells to constitutively express chemokine genes, which may suggest an important role for chemokines during brain development. Furthermore, TLTF-induced chemokine expression in astrocytes and neurons indicate the capacity of TLTF to provoke neuroinflammation in the brain, which may have important therapeutic implications for the neurological manifestations of African trypanosomiasis.
Bakhiet
Moiz
M
Center for Infectious Medicine, Karolinska Institute, Huddinge University Hospital, (F-82), SE-141 86, Stockholm, Sweden. moiz.bakhiet@medhs.ki.se
Mousa
Alyaa
A
Seiger
Ake
A
Andersson
Jan
J
D001253:Astrocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000276:immunology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology / Q000276:immunology*; D015800:Protozoan Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation
D018925:Chemokines; D008070:Lipopolysaccharides; D015800:Protozoan Proteins; D012333:RNA, Messenger; C107172:T lymphocyte triggering factor, Trypanosoma brucei