Murine mammary carcinoma cells and CD11c(+) dendritic cells elicit distinct responses to lipopolysaccharide and exhibit differential expression of genes required for TLR4 signaling.
Although TLR are often studied on DC because of their ability to bridge innate and adaptive defenses, TLR are also expressed by epithelial cells. Because the majority of cancers are carcinomas, and thus of epithelial origin, we wanted to know whether a carcinoma and DC responded similarly to a TLR agonist. We found the mammary carcinoma 4T1 and CD11c(+) DC both secreted proinflammatory chemokines in response to the TLR4 agonist lipopolysaccharide (LPS). However a clear dichotomy existed. DC, but not 4T1 secreted IL-1β, TNF-α, and upregulated CD80 and CD86 expression following LPS treatment. A potential reason for differential responsiveness was that DC expressed greater levels of TLR4, CD14, Myd88, and TRAM. Despite the low level of TLR signaling proteins, the carcinoma were able to elicit a range of responses contingent upon the source, dose, length, and frequency of TLR agonist treatment. Thus, carcinoma and DC are distinctly responsive to LPS.
Palha De Sousa
Chiquita
C
Department of Biology, Lafayette College, Easton, PA 18042, USA.
Blum
Christopher M
CM
Sgroe
Erica P
EP
Crespo
Alexander M
AM
Kurt
Robert A
RA
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010457:Peptidoglycan / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000378:metabolism*
D015703:Antigens, CD; D039521:CD11c Antigen; D018925:Chemokines; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010457:Peptidoglycan; D018123:Receptors, Interleukin; C476416:Ticam2 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4