PMID- 8843914
OWN - NLM
STAT- MEDLINE
DCOM- 19961106
LR  - 20111117
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 37
IP  - 11
DP  - 1996 Oct
TI  - Herpes simplex virus type 1 alters transcript levels of tumor necrosis 
      factor-alpha and interleukin-6 in retinal glial cells.
PG  - 2302-12
AB  - PURPOSE: Studies were performed to determine whether retinal Muller cells 
      transcribe genes for the proinflammatory cytokines interleukin-6 (IL-6) and tumor 
      necrosis factor-alpha (TNF alpha). Isolated murine retinas were used to test 
      whether these cytokines were upregulated in the retina in vivo after anterior 
      chamber inoculation of herpes simplex virus type 1 (HSV-1). The effects of 
      exposure to HSV-1 or interferon-gamma (IFN gamma) on transcript levels of these 
      cytokines in cultured retinal glia also were examined. METHODS: In situ 
      hybridization (ISH) using digoxigenin (DIG)-labeled RNA probes was used to 
      localize mRNA for IL-6 and TNF alpha in cultured retinal glial cells. Changes in 
      IL-6 and TNF alpha relative transcript levels were assessed in cultured retinal 
      glial cells using a semiquantitative approach comprised of reverse 
      transcription-polymerase chain reaction (RT-PCR) assay at low amplification cycle 
      number followed by slot blotting and hybridization with DIG-labeled internal 
      sequence probes. In the murine model of herpetic retinitis, the same methods were 
      used to compare temporal changes in relative cytokine transcript levels in 
      retinas isolated from eyes 1 to 7 days after anterior chamber injection of live 
      HSV-1 (KOS strain; 2 x 10(4) pfu/eye) or buffer with levels in retinas isolated 
      from normal, uninjected eyes. Densitometry was used to quantify relative signal 
      changes obtained with serial diluted samples in slot blot assays. Cytokine signal 
      was normalized to hypoxanthine phosphoribosyl transferase signal obtained from 
      the same cDNA samples. RESULTS: Under baseline culture conditions, ISH and RT-PCR 
      indicated that both IL-6 and TNF alpha were transcribed by cultured retinal glia. 
      In vitro exposure to either viral (HSV-1) or inflammatory (IFN gamma) stimulants 
      increased levels of these transcripts in a time-dependent manner. Peak TNF alpha 
      mRNA levels were detected 4 hours after exposure to HSV, whereas IL-6 peaked 4 
      hours later (increases of 10.3 and 8.7 times over baseline, respectively). 
      Differential increases in TNF alpha and IL-6 transcript levels were detected in 
      retinas isolated from BALB/c mice that received anterior chamber injections of 
      either HSV-1 or Hanks' balanced salt solution (HBSS). By day 3 after HSV-1 
      injection, increases of 4.5-fold in TNF alpha and 17-fold in IL-6 were detected, 
      whereas substantially smaller changes in TNF alpha and IL-6 (1.5-fold and 
      6.3-fold, respectively) were observed in HBSS-injected eyes Virus-induced changes 
      in TNF alpha mRNA levels occurred slightly earlier than for IL-6 because maximal 
      levels of TNF alpha were detected 2 to 3 days after infection, but IL-6 peaked at 
      day 3. CONCLUSIONS: Cultured retinal glial cells exhibit upregulated TNF alpha 
      and IL-6 transcript levels after exposure to virus or inflammatory mediators. 
      HSV-1 infection of the anterior segment of the mouse eye markedly upregulates TNF 
      alpha and IL-6 mRNA levels compared to smaller responses to nonspecific 
      inflammation. Taken together, these results identify retinal Muller cells as an 
      intraretinal source of TNF alpha and IL-6 and support the potential of these 
      resident cells to act as intraretinal modulators of immune and inflammatory 
      responses.
FAU - Drescher, K M
AU  - Drescher KM
AD  - Department of Molecular Microbiology and Immunology, Johns Hopkins University 
      School of Hygiene and Public Health, Baltimore, Maryland 21287-9142, USA.
FAU - Whittum-Hudson, J A
AU  - Whittum-Hudson JA
LA  - eng
GR  - 5T2 EY07047/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cytokines/genetics/*metabolism
MH  - Eye Infections, Viral/*metabolism
MH  - Female
MH  - Herpes Simplex/*metabolism
MH  - *Herpesvirus 1, Human
MH  - In Situ Hybridization
MH  - Interferon-gamma
MH  - Interleukin-6/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neuroglia/*metabolism
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/metabolism
MH  - Recombinant Proteins
MH  - Retina/cytology/*metabolism
MH  - Retinitis/*metabolism/virology
MH  - *Transcription, Genetic
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
MH  - Up-Regulation
EDAT- 1996/10/01 00:00
MHDA- 1996/10/01 00:01
CRDT- 1996/10/01 00:00
PHST- 1996/10/01 00:00 [pubmed]
PHST- 1996/10/01 00:01 [medline]
PHST- 1996/10/01 00:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 1996 Oct;37(11):2302-12.